{"entity": "researcher", "timestamp": "2026-07-18T02:26:14.427Z", "family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "affiliations": ["Genome Engineering Zebrafish Facility, Science For Life Laboratory, Uppsala University, SE-752 36 Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd"}}, "publications": [{"entity": "publication", "iuid": "6b2cc1f6c66b4fe5baafa285bceb1e14", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6b2cc1f6c66b4fe5baafa285bceb1e14.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6b2cc1f6c66b4fe5baafa285bceb1e14"}}, "title": "Chondroitin/dermatan sulfate glycosyltransferase genes are essential for craniofacial development.", "authors": [{"family": "Habicher", "given": "Judith", "initials": "J", "orcid": "0000-0002-8691-8650", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1415531d8fe4ea7991035665c58e8ba.json"}}, {"family": "Varshney", "given": "Gaurav K", "initials": "GK", "orcid": "0000-0002-0429-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5b107029a9844de8b103873831b54f2.json"}}, {"family": "Waldmann", "given": "Laura", "initials": "L", "orcid": "0000-0002-3619-0796", "researcher": {"href": "https://publications.scilifelab.se/researcher/360d0e0c567f4bf1ae6967f4dedfad1a.json"}}, {"family": "Snitting", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9704-6336", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f99ef381b0b483ea34d05742e38314c.json"}}, {"family": "Allalou", "given": "Amin", "initials": "A", "orcid": "0000-0003-4028-8443", "researcher": {"href": "https://publications.scilifelab.se/researcher/98fffa8e99254fb597bf07dea61d8e37.json"}}, {"family": "Zhang", "given": "Hanqing", "initials": "H"}, {"family": "Ghanem", "given": "Abdurrahman", "initials": "A", "orcid": "0000-0002-4388-6222", "researcher": {"href": "https://publications.scilifelab.se/researcher/08da887bb77d4024a363c81876f3c353.json"}}, {"family": "\u00d6hman M\u00e4gi", "given": "Caroline", "initials": "C", "orcid": "0000-0003-2709-9541", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e91cc9f7f5e4e6da24c6f7f9b4437f1.json"}}, {"family": "Dierker", "given": "Tabea", "initials": "T", "orcid": "0000-0003-1991-2723", "researcher": {"href": "https://publications.scilifelab.se/researcher/51eabac50a584797ba34d0405389eb94.json"}}, {"family": "Kjell\u00e9n", "given": "Lena", "initials": "L"}, {"family": "Burgess", "given": "Shawn M", "initials": "SM", "orcid": "0000-0003-1147-0596", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf85532f49bc4208b7e456d4ee2e8f76.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "issn-l": "1553-7390", "volume": "18", "issue": "2", "pages": "e1010067"}, "abstract": "Chondroitin/dermatan sulfate (CS/DS) proteoglycans are indispensable for animal development and homeostasis but the large number of enzymes involved in their biosynthesis have made CS/DS function a challenging problem to study genetically. In our study, we generated loss-of-function alleles in zebrafish genes encoding CS/DS biosynthetic enzymes and characterized the effect on development in single and double mutants. Homozygous mutants in chsy1, csgalnact1a, csgalnat2, chpfa, ust and chst7, respectively, develop to adults. However, csgalnact1a-/- fish develop distinct craniofacial defects while the chsy1-/- skeletal phenotype is milder and the remaining mutants display no gross morphological abnormalities. These results suggest a high redundancy for the CS/DS biosynthetic enzymes and to further reduce CS/DS biosynthesis we combined mutant alleles. The craniofacial phenotype is further enhanced in csgalnact1a-/-;chsy1-/- adults and csgalnact1a-/-;csgalnact2-/- larvae. While csgalnact1a-/-;csgalnact2-/- was the most affected allele combination in our study, CS/DS is still not completely abolished. Transcriptome analysis of chsy1-/-, csgalnact1a-/- and csgalnact1a-/-;csgalnact2-/- larvae revealed that the expression had changed in a similar way in the three mutant lines but no differential expression was found in any of fifty GAG biosynthesis enzymes identified. Thus, zebrafish larvae do not increase transcription of GAG biosynthesis genes as a consequence of decreased CS/DS biosynthesis. The new zebrafish lines develop phenotypes similar to clinical characteristics of several human congenital disorders making the mutants potentially useful to study disease mechanisms and treatment.", "doi": "10.1371/journal.pgen.1010067", "pmid": "35192612", "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8896900"}, {"db": "pii", "key": "PGENETICS-D-21-00836"}], "notes": [], "created": "2022-12-01T15:56:03.295Z", "modified": "2022-12-01T15:56:12.937Z"}, {"entity": "publication", "iuid": "d23f81c368e94e89aaf7b3ffaf6f29bc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d23f81c368e94e89aaf7b3ffaf6f29bc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d23f81c368e94e89aaf7b3ffaf6f29bc"}}, "title": "Heparan Sulfate Biosynthesis in Zebrafish.", "authors": [{"family": "Filipek-G\u00f3rniok", "given": "Beata", "initials": "B", "orcid": "0000-0002-6757-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/11f0b7b3e0b045f082d2aff1dd23ec0e.json"}}, {"family": "Habicher", "given": "Judith", "initials": "J"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Kjell\u00e9n", "given": "Lena", "initials": "L"}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "J. Histochem. Cytochem.", "issn": "1551-5044", "volume": "69", "issue": "1", "pages": "49-60", "issn-l": "0022-1554"}, "abstract": "The biosynthesis of heparan sulfate (HS) proteoglycans occurs in the Golgi compartment of cells and will determine the sulfation pattern of HS chains, which in turn will have a large impact on the biological activity of the proteoglycans. Earlier studies in mice have demonstrated the importance of HS for embryonic development. In this review, the enzymes participating in zebrafish HS biosynthesis, along with a description of enzyme mutants available for functional studies, are presented. The consequences of the zebrafish genome duplication and maternal transcript contribution are briefly discussed as are the possibilities of CRISPR/Cas9 methodologies to use the zebrafish model system for studies of biosynthesis as well as proteoglycan biology.", "doi": "10.1369/0022155420973980", "pmid": "33216642", "labels": {"Genome Engineering Zebrafish": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7780192"}], "notes": [], "created": "2021-01-12T09:33:36.164Z", "modified": "2021-11-10T12:28:04.027Z"}, {"entity": "publication", "iuid": "ee18a396f79f4e90a668a1318fc73ed8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee18a396f79f4e90a668a1318fc73ed8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee18a396f79f4e90a668a1318fc73ed8"}}, "title": "Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish.", "authors": [{"family": "Banote", "given": "Rakesh Kumar", "initials": "RK"}, {"family": "Chebli", "given": "Jasmine", "initials": "J"}, {"family": "\u015eat\u0131r", "given": "Tu\u011f\u00e7e Munise", "initials": "TM"}, {"family": "Varshney", "given": "Gaurav K", "initials": "GK", "orcid": "0000-0002-0429-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5b107029a9844de8b103873831b54f2.json"}}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Burgess", "given": "Shawn M", "initials": "SM", "orcid": "0000-0003-1147-0596", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf85532f49bc4208b7e456d4ee2e8f76.json"}}, {"family": "Abramsson", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-4715-9225", "researcher": {"href": "https://publications.scilifelab.se/researcher/7abde12dab2e4d338bc6e55933f07531.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-06-23", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "10127", "issn-l": "2045-2322"}, "abstract": "Understanding the biological function of amyloid beta (A\u03b2) precursor protein (APP) beyond its role in Alzheimer's disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP orthologue, Appb, is strongly expressed during early development but thus far has only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2 dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage. Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of the app family member, appa, was also found to be altered in appb mutants. Taken together, we show that appb is involved in the initial development of zebrafish by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might then be compensated for by other app family members to maintain normal development.", "doi": "10.1038/s41598-020-66584-8", "pmid": "32576936", "labels": {"Genome Engineering Zebrafish": "Collaborative", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7311384"}, {"db": "pii", "key": "10.1038/s41598-020-66584-8"}], "notes": [], "created": "2020-06-24T09:03:55.674Z", "modified": "2023-02-16T08:03:52.996Z"}, {"entity": "publication", "iuid": "99480ec8afcc46d399c2d2bf162d97fd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/99480ec8afcc46d399c2d2bf162d97fd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/99480ec8afcc46d399c2d2bf162d97fd"}}, "title": "Zebrafish embryo as a replacement model for initial biocompatibility studies of biomaterials and drug delivery systems.", "authors": [{"family": "Rothenb\u00fccher", "given": "Theresa S P", "initials": "TSP"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Gibbs", "given": "David", "initials": "D"}, {"family": "Engqvist", "given": "H\u00e5kan", "initials": "H"}, {"family": "Persson", "given": "Cecilia", "initials": "C", "orcid": "0000-0001-6663-6536", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fb6fe3555374aec90b2a8b9dfd8016b.json"}}, {"family": "Hulsart-Billstr\u00f6m", "given": "Gry", "initials": "G", "orcid": "0000-0003-2422-831X", "researcher": {"href": "https://publications.scilifelab.se/researcher/52fbfff04d284491a9dc55414e7a3240.json"}}], "type": "journal article", "published": "2019-12-00", "journal": {"title": "Acta Biomater", "issn": "1878-7568", "volume": "100", "issue": null, "pages": "235-243", "issn-l": "1742-7061"}, "abstract": "The development of new biomaterials and drug delivery systems necessitates animal experimentation to demonstrate biocompatibility and therapeutic efficacy. Reduction and replacement of the requirement to conduct experiment using full-grown animals has been achieved through utilising zebrafish embryos, a promising bridge model between in vitro and in vivo research. In this review, we consider how zebrafish embryos have been utilised to test both the biocompatibility of materials developed to interact with the human body and drug release studies. Furthermore, we outline the advantages and limitations of this model and review legal and ethical issues. We anticipate increasing application of the zebrafish model for biomaterial evaluation in the near future. STATEMENT OF SIGNIFICANCE: This review aims to evaluate the potential application and suitability of the zebrafish model in the development of biomaterials and drug delivery systems. It creates scientific impact and interest because replacement models are desirable to the society and the scientific community. The continuous development of biomaterials calls for the need to provide solutions for biological testing. This review covers the topic of how the FET model can be applied to evaluate biocompatibility. Further, it explores the zebrafish from the wild-type to the mutant form, followed by a discussion about the ethical considerations and concerns when using the FET model.", "doi": "10.1016/j.actbio.2019.09.038", "pmid": "31585201", "labels": {"Genome Engineering Zebrafish": null}, "xrefs": [{"db": "pii", "key": "S1742-7061(19)30659-2"}], "notes": [], "created": "2021-01-12T09:32:53.682Z", "modified": "2021-07-06T14:27:46.369Z"}, {"entity": "publication", "iuid": "680565f978934fedb42fa5ba80bbc4fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/680565f978934fedb42fa5ba80bbc4fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/680565f978934fedb42fa5ba80bbc4fe"}}, "title": "The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension.", "authors": [{"family": "Morikawa", "given": "Masato", "initials": "M", "orcid": "0000-0002-6191-7176", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ff787ffdf444850b9e4906c8c95fa92.json"}}, {"family": "Mitani", "given": "Yoshihide", "initials": "Y"}, {"family": "Holmborn", "given": "Katarina", "initials": "K"}, {"family": "Kato", "given": "Taichi", "initials": "T", "orcid": "0000-0001-7084-4565", "researcher": {"href": "https://publications.scilifelab.se/researcher/a737a920309943d48f55ccbedd02fd6c.json"}}, {"family": "Koinuma", "given": "Daizo", "initials": "D", "orcid": "0000-0001-5611-2122", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf10583b944248b19c07772a0b364684.json"}}, {"family": "Maruyama", "given": "Junko", "initials": "J"}, {"family": "Vasilaki", "given": "Eleftheria", "initials": "E", "orcid": "0000-0001-6743-8523", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b2aa70aa68a48f7870b664caf9ca3b3.json"}}, {"family": "Sawada", "given": "Hirofumi", "initials": "H", "orcid": "0000-0001-8069-5751", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf45576856c9452888d08842b88669ca.json"}}, {"family": "Kobayashi", "given": "Mai", "initials": "M"}, {"family": "Ozawa", "given": "Takayuki", "initials": "T"}, {"family": "Morishita", "given": "Yasuyuki", "initials": "Y"}, {"family": "Bessho", "given": "Yasumasa", "initials": "Y"}, {"family": "Maeda", "given": "Shingo", "initials": "S", "orcid": "0000-0002-2737-3902", "researcher": {"href": "https://publications.scilifelab.se/researcher/152d321d11944b3ca9eb3ef387e70cd0.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Aburatani", "given": "Hiroyuki", "initials": "H", "orcid": "0000-0003-0438-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bce060d4ff8446dbafc86bf5e3a001d.json"}}, {"family": "Kageyama", "given": "Ryoichiro", "initials": "R"}, {"family": "Maruyama", "given": "Kazuo", "initials": "K", "orcid": "0000-0003-3685-6348", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd2eaad9217344a89fcc666951831e75.json"}}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f705f7c509904a1db721ace2267ca48f.json"}}, {"family": "Miyazono", "given": "Kohei", "initials": "K", "orcid": "0000-0001-7341-0172", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a14a58f628d435a94ad9540478117cb.json"}}], "type": "journal article", "published": "2019-11-12", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "12", "issue": "607", "pages": "eaay4430", "issn-l": "1945-0877"}, "abstract": "Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of Atoh8 did not cause an arteriovenous malformation-like phenotype, which may arise because of dysregulated Notch signaling. In contrast, Atoh8-deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, ATOH8 expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2\u03b1 (HIF-2\u03b1) and decreased its abundance, leading to reduced induction of HIF-2\u03b1 target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.", "doi": "10.1126/scisignal.aay4430", "pmid": "31719172", "labels": {"Genome Engineering Zebrafish": "Collaborative"}, "xrefs": [{"db": "pii", "key": "12/607/eaay4430"}, {"db": "pmc", "key": "PMC6908447"}, {"db": "mid", "key": "EMS85032"}], "notes": [], "created": "2019-12-02T16:11:40.604Z", "modified": "2021-06-16T16:18:32.543Z"}, {"entity": "publication", "iuid": "46cd7cf01fbc4ddf87f7503100fbaaab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/46cd7cf01fbc4ddf87f7503100fbaaab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/46cd7cf01fbc4ddf87f7503100fbaaab"}}, "title": "TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish.", "authors": [{"family": "Gudmundsson", "given": "Sanna", "initials": "S", "orcid": "0000-0002-2332-074X", "researcher": {"href": "https://publications.scilifelab.se/researcher/adb097c987504b2ca309e5f4e1cea5d2.json"}}, {"family": "Wilbe", "given": "Maria", "initials": "M"}, {"family": "Filipek-G\u00f3rniok", "given": "Beata", "initials": "B", "orcid": "0000-0002-6757-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/11f0b7b3e0b045f082d2aff1dd23ec0e.json"}}, {"family": "Molin", "given": "Anna-Maja", "initials": "A"}, {"family": "Ekvall", "given": "Sara", "initials": "S"}, {"family": "Johansson", "given": "Josefin", "initials": "J", "orcid": "0000-0002-5152-4096", "researcher": {"href": "https://publications.scilifelab.se/researcher/e568827124304b769a3f336d76b6954e.json"}}, {"family": "Allalou", "given": "Amin", "initials": "A"}, {"family": "Gylje", "given": "Hans", "initials": "H"}, {"family": "Kalscheuer", "given": "Vera M", "initials": "VM", "orcid": "0000-0001-6898-3259", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb8107a11ed144bc8f4c236042f9bc8c.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "M"}], "type": "journal article", "published": "2019-07-24", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "9", "issue": "1", "pages": "10730"}, "abstract": "The TATA-box binding protein associated factor 1 (TAF1) protein is a key unit of the transcription factor II D complex that serves a vital function during transcription initiation. Variants of TAF1 have been associated with neurodevelopmental disorders, but TAF1's molecular functions remain elusive. In this study, we present a five-generation family affected with X-linked intellectual disability that co-segregated with a TAF1 c.3568C>T, p.(Arg1190Cys) variant. All affected males presented with intellectual disability and dysmorphic features, while heterozygous females were asymptomatic and had completely skewed X-chromosome inactivation. We investigated the role of TAF1 and its association to neurodevelopment by creating the first complete knockout model of the TAF1 orthologue in zebrafish. A crucial function of human TAF1 during embryogenesis can be inferred from the model, demonstrating that intact taf1 is essential for embryonic development. Transcriptome analysis of taf1 zebrafish knockout revealed enrichment for genes associated with neurodevelopmental processes. In conclusion, we propose that functional TAF1 is essential for embryonic development and specifically neurodevelopmental processes.", "doi": "10.1038/s41598-019-46632-8", "pmid": "31341187", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Service", "Genome Engineering Zebrafish": "Collaborative", "Bioinformatics Support and Infrastructure": "Service", "BioImage Informatics": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-019-46632-8"}, {"db": "pmc", "key": "PMC6656882"}], "notes": [], "created": "2019-11-29T13:27:12.056Z", "modified": "2024-01-16T13:48:44.102Z"}, {"entity": "publication", "iuid": "a366fe5139384ade916225960fa5d8e1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a366fe5139384ade916225960fa5d8e1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a366fe5139384ade916225960fa5d8e1"}}, "title": "Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis", "authors": [{"family": "Bandaru", "given": "Manoj K", "initials": "MK", "orcid": "0000-0002-5664-6711", "researcher": {"href": "https://publications.scilifelab.se/researcher/024e44747cdd4f5f85c1cf61d3320b09.json"}}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "Ranefall", "given": "Petter", "initials": "P", "orcid": "0000-0002-6699-4015", "researcher": {"href": "https://publications.scilifelab.se/researcher/4332883c0058421f8dfb85406ec03524.json"}}, {"family": "von der Heyde", "given": "Benedikt", "initials": "B", "orcid": "0000-0002-9889-4027", "researcher": {"href": "https://publications.scilifelab.se/researcher/803c0e0639174a50b59ae597802e824f.json"}}, {"family": "Mazzaferro", "given": "Eugenia", "initials": "E"}, {"family": "Klingstr\u00f6m", "given": "Tiffany", "initials": "T"}, {"family": "Masiero", "given": "Mauro", "initials": "M"}, {"family": "Dethlefsen", "given": "Olga", "initials": "O"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Larsson", "given": "Anders", "initials": "A"}, {"family": "Brooke", "given": "Hannah L", "initials": "HL"}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d712cc087d344b15ab9a7971640acebe.json"}}], "type": "posted-content", "published": "2018-12-20", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/502674", "pmid": null, "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-08T07:55:34.310Z", "modified": "2025-12-18T20:08:39.251Z"}, {"entity": "publication", "iuid": "fbf2fa0eb8664f2399794717d866aeb7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fbf2fa0eb8664f2399794717d866aeb7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fbf2fa0eb8664f2399794717d866aeb7"}}, "title": "Large-scale validation of zebrafish larvae as a model system for genetic screens in dyslipidaemia, atherosclerosis and coronary artery disease", "authors": [{"family": "Bandaru", "given": "Manoj", "initials": "M", "orcid": "0000-0002-5664-6711", "researcher": {"href": "https://publications.scilifelab.se/researcher/024e44747cdd4f5f85c1cf61d3320b09.json"}}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "Ranefall", "given": "Petter", "initials": "P", "orcid": "0000-0002-6699-4015", "researcher": {"href": "https://publications.scilifelab.se/researcher/4332883c0058421f8dfb85406ec03524.json"}}, {"family": "von der Heyde", "given": "Benedikt", "initials": "B", "orcid": "0000-0002-9889-4027", "researcher": {"href": "https://publications.scilifelab.se/researcher/803c0e0639174a50b59ae597802e824f.json"}}, {"family": "Klingstr\u00f6m", "given": "Tiffany", "initials": "T"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Larsson", "given": "Anders", "initials": "A"}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d712cc087d344b15ab9a7971640acebe.json"}}], "type": null, "published": "2017-10-17", "journal": {"volume": null, "issn": null, "issue": null, "pages": null, "title": "ASHG 2017 Annual Meeting - The American Society of Human Genetics", "issn-l": null}, "abstract": "Background: Genome-wide association studies have identified 77 loci that are robustly associated with coronary artery disease (CAD). In all but a few of these loci the causal genes and mechanisms remain unknown. Results from small-scale studies suggest that zebrafish larvae represent a promising model system for genetic screens in dyslipidemia, early-stage atherosclerosis and CAD. We aim to confirm or refute these results in a large-scale study, expand the phenotypic pipeline, and increase the throughput.\r\n\r\nMethods: At the core of our setup is an automated positioning and imaging system that allows visualization and quantification of atherogenic traits in ~100 zebrafish larvae per day at 10 days post-fertilization, by making use of fluorescent transgenes and dyes. We used a three-tiered approach to validate the zebrafish model system: 1) a dietary intervention to examine the effect of overfeeding and cholesterol supplementation (N=2193); 2) a treatment regime with atorvastatin and ezetimibe (N=956); and 3) a genetic screen for zebrafish orthologues of LDLR, PCSK9, APOB and APOE using a multiplex CRISPR-Cas9 approach (N=2x384). After imaging, whole-body lipid and glucose levels were assessed using enzymatic assays, and CRISPR-Cas9 target sites were sequenced on a MiSeq.\r\n\r\nResults: Overfeeding and cholesterol supplementation have independent pro-atherogenic effects, including elevated total cholesterol and triglyceride levels, more vascular deposition of lipids and oxidized LDLc, and more co-localization of lipids with macrophages and neutrophils. Treatment with atorvastatin and ezetimibe results in lower whole-body total cholesterol, LDLc and triglyceride levels, as well as in less vascular lipid deposition and less co-localization of lipids and macrophages. Finally, mutations in APOE orthologues result in higher whole-body LDLc levels and more co-localization of lipids with macrophages or neutrophils compared with wildtypes. Mutations in APOB orthologues tend to result in higher LDLc levels, more vascular lipid deposition, and more co-localizing lipids and neutrophils. Treatment with lipid lowering drugs and mutations in pcsk9 both result in higher whole-body glucose levels. Data from all larvae combined show that atherosclerosis in 10-day-old zebrafish larvae is mainly driven by higher triglyceride but not LDLc levels.\r\n\r\nConclusion: Zebrafish larvae can be used to systematically identify and characterize causal genes for CAD.", "doi": null, "pmid": null, "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-11-10T08:53:10.829Z", "modified": "2025-11-17T09:58:04.394Z"}, {"entity": "publication", "iuid": "1114e0886af841b58cd91654ec49c796", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1114e0886af841b58cd91654ec49c796.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1114e0886af841b58cd91654ec49c796"}}, "title": "A high-throughput functional genomics workflow based on CRISPR/Cas9-mediated targeted mutagenesis in zebrafish.", "authors": [{"family": "Varshney", "given": "Gaurav K", "initials": "GK"}, {"family": "Carrington", "given": "Blake", "initials": "B"}, {"family": "Pei", "given": "Wuhong", "initials": "W"}, {"family": "Bishop", "given": "Kevin", "initials": "K"}, {"family": "Chen", "given": "Zelin", "initials": "Z"}, {"family": "Fan", "given": "Chunxin", "initials": "C"}, {"family": "Xu", "given": "Lisha", "initials": "L"}, {"family": "Jones", "given": "Marypat", "initials": "M"}, {"family": "LaFave", "given": "Matthew C", "initials": "MC", "orcid": "0000-0001-9165-041X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bc2b970f77c4479886070a56418227f.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Sood", "given": "Raman", "initials": "R"}, {"family": "Burgess", "given": "Shawn M", "initials": "SM", "orcid": "0000-0003-1147-0596", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf85532f49bc4208b7e456d4ee2e8f76.json"}}], "type": "journal article", "published": "2016-12-00", "journal": {"volume": "11", "issn": "1750-2799", "issue": "12", "pages": "2357-2375", "title": "Nat Protoc", "issn-l": null}, "abstract": "The zebrafish is a popular model organism for studying development and disease, and genetically modified zebrafish provide an essential tool for functional genomic studies. Numerous publications have demonstrated the efficacy of gene targeting in zebrafish using CRISPR/Cas9, and they have included descriptions of a variety of tools and methods for guide RNA synthesis and mutant identification. However, most of the published techniques are not readily scalable to increase throughput. We recently described a CRISPR/Cas9-based high-throughput mutagenesis and phenotyping pipeline in zebrafish. Here, we present a complete workflow for this pipeline, including target selection; cloning-free single-guide RNA (sgRNA) synthesis; microinjection; validation of the target-specific activity of the sgRNAs; founder screening to identify germline-transmitting mutations by fluorescence PCR; determination of the exact lesion by Sanger or next-generation sequencing (including software for analysis); and genotyping in the F1 or subsequent generations. Using these methods, sgRNAs can be evaluated in 3 d, zebrafish germline-transmitting mutations can be identified within 3 months and stable lines can be established within 6 months. Realistically, two researchers can target tens to hundreds of genes per year using this protocol.", "doi": "10.1038/nprot.2016.141", "pmid": "27809318", "labels": {"Genome Engineering Zebrafish": "Technology development"}, "xrefs": [{"db": "pii", "key": "nprot.2016.141"}, {"db": "pmc", "key": "PMC5630457"}, {"db": "mid", "key": "NIHMS905110"}], "notes": [], "created": "2017-05-08T07:59:55.363Z", "modified": "2021-07-06T14:27:46.329Z"}, {"entity": "publication", "iuid": "4ef42a1207e84cca8d2f102efdd6e2c2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4ef42a1207e84cca8d2f102efdd6e2c2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4ef42a1207e84cca8d2f102efdd6e2c2"}}, "title": "Fish from Head to Tail: The 9th European Zebrafish Meeting in Oslo.", "authors": [{"family": "Griffiths", "given": "Gareth", "initials": "G"}, {"family": "M\u00fcller", "given": "Ferenc", "initials": "F"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Patton", "given": "E Elizabeth", "initials": "EE"}, {"family": "Gj\u00f8en", "given": "Tor", "initials": "T"}, {"family": "Lobert", "given": "Viola H\u00e9l\u00e8ne", "initials": "VH"}, {"family": "Winther-Larsen", "given": "Hanne Cecilie", "initials": "HC"}, {"family": "Mullins", "given": "Mary", "initials": "M"}, {"family": "Joly", "given": "Jean-Stephane", "initials": "JS"}, {"family": "Weltzien", "given": "Finn-Arne", "initials": "FA"}, {"family": "Press", "given": "Charles McLean", "initials": "CM"}, {"family": "Alestr\u00f6m", "given": "Peter", "initials": "P"}], "type": "congresses", "published": "2016-04-00", "journal": {"volume": "13", "issn": "1557-8542", "issue": "2", "pages": "132-137", "title": "Zebrafish", "issn-l": "1545-8547"}, "abstract": "The 9th European Zebrafish Meeting took place recently in Oslo (June 28-July 2, 2015). A total of 650 participants came to hear the latest research news focused on the zebrafish, Danio rerio, and to its distant evolutionary relative medaka, Oryzias latipes. The packed program included keynote and plenary talks, short oral presentations and poster sessions, workshops, and strategic discussions. The meeting was a great success and revealed dramatically how important the zebrafish in particular has become as a model system for topics, such as developmental biology, functional genomics, biomedicine, toxicology, and drug development. A new emphasis was given to its potential as a model for aquaculture, a topic of great economic interest to the host country Norway and for the future global food supply in general. Zebrafish husbandry as well as its use in teaching were also covered in separate workshops. As has become a tradition in these meetings, there was a well-attended Wellcome Trust Sanger Institute and ZFIN workshop focused on Zebrafish Genome Resources on the first day. The full EZM 2015 program with abstracts can be read and downloaded from the EZM 2015 Web site zebrafish2015.org .", "doi": "10.1089/zeb.2015.1212", "pmid": "26859625", "labels": {"Genome Engineering Zebrafish": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-05-03T13:02:38.353Z", "modified": "2021-07-06T14:27:46.353Z"}, {"entity": "publication", "iuid": "99eb2c94bbb641f49c2f2acf2fc1a558", "links": {"self": {"href": "https://publications.scilifelab.se/publication/99eb2c94bbb641f49c2f2acf2fc1a558.json"}, "display": {"href": "https://publications.scilifelab.se/publication/99eb2c94bbb641f49c2f2acf2fc1a558"}}, "title": "CRISPRz: a database of zebrafish validated sgRNAs.", "authors": [{"family": "Varshney", "given": "Gaurav K", "initials": "GK"}, {"family": "Zhang", "given": "Suiyuan", "initials": "S"}, {"family": "Pei", "given": "Wuhong", "initials": "W"}, {"family": "Adomako-Ankomah", "given": "Ashrifia", "initials": "A"}, {"family": "Fohtung", "given": "Jacob", "initials": "J"}, {"family": "Schaffer", "given": "Katherine", "initials": "K"}, {"family": "Carrington", "given": "Blake", "initials": "B"}, {"family": "Maskeri", "given": "Anoo", "initials": "A"}, {"family": "Slevin", "given": "Claire", "initials": "C"}, {"family": "Wolfsberg", "given": "Tyra", "initials": "T"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Sood", "given": "Raman", "initials": "R", "orcid": "0000-0001-5565-662X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b409d94e997c4b6d8a0cf915e884a893.json"}}, {"family": "Burgess", "given": "Shawn M", "initials": "SM"}], "type": "journal article", "published": "2016-01-04", "journal": {"volume": "44", "issn": "1362-4962", "issue": "D1", "pages": "D822-D826", "title": "Nucleic Acids Res.", "issn-l": "0305-1048"}, "abstract": "CRISPRz (http://research.nhgri.nih.gov/CRISPRz/) is a database of CRISPR/Cas9 target sequences that have been experimentally validated in zebrafish. Programmable RNA-guided CRISPR/Cas9 has recently emerged as a simple and efficient genome editing method in various cell types and organisms, including zebrafish. Because the technique is so easy and efficient in zebrafish, the most valuable asset is no longer a mutated fish (which has distribution challenges), but rather a CRISPR/Cas9 target sequence to the gene confirmed to have high mutagenic efficiency. With a highly active CRISPR target, a mutant fish can be quickly replicated in any genetic background anywhere in the world. However, sgRNA's vary widely in their activity and models for predicting target activity are imperfect. Thus, it is very useful to collect in one place validated CRISPR target sequences with their relative mutagenic activities. A researcher could then select a target of interest in the database with an expected activity. Here, we report the development of CRISPRz, a database of validated zebrafish CRISPR target sites collected from published sources, as well as from our own in-house large-scale mutagenesis project. CRISPRz can be searched using multiple inputs such as ZFIN IDs, accession number, UniGene ID, or gene symbols from zebrafish, human and mouse.", "doi": "10.1093/nar/gkv998", "pmid": "26438539", "labels": {"Genome Engineering Zebrafish": "Technology development"}, "xrefs": [{"db": "pii", "key": "gkv998"}, {"db": "pmc", "key": "PMC4702947"}], "notes": [], "created": "2017-05-03T13:02:38.646Z", "modified": "2021-07-06T14:27:46.376Z"}, {"entity": "publication", "iuid": "71b0cc52b64d44fd86a7e9431f2451a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/71b0cc52b64d44fd86a7e9431f2451a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/71b0cc52b64d44fd86a7e9431f2451a1"}}, "title": "Spinal deformity in aged zebrafish is accompanied by degenerative changes to their vertebrae that resemble osteoarthritis.", "authors": [{"family": "Hayes", "given": "Anthony J", "initials": "AJ"}, {"family": "Reynolds", "given": "Scott", "initials": "S"}, {"family": "Nowell", "given": "Mari A", "initials": "MA"}, {"family": "Meakin", "given": "Lee B", "initials": "LB"}, {"family": "Habicher", "given": "Judith", "initials": "J"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Bashford", "given": "Andrew", "initials": "A"}, {"family": "Caterson", "given": "Bruce", "initials": "B"}, {"family": "Hammond", "given": "Chrissy L", "initials": "CL"}], "type": "journal article", "published": "2013-09-24", "journal": {"volume": "8", "issn": "1932-6203", "issue": "9", "pages": "e75787", "title": "PLoS ONE", "issn-l": "1932-6203"}, "abstract": "Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking age-related changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.", "doi": "10.1371/journal.pone.0075787", "pmid": "24086633", "labels": {"Genome Engineering Zebrafish": null}, "xrefs": [{"db": "pii", "key": "PONE-D-13-26599"}, {"db": "pmc", "key": "PMC3782452"}], "notes": [], "created": "2017-05-04T15:03:44.039Z", "modified": "2021-07-06T14:27:46.361Z"}, {"entity": "publication", "iuid": "4cd28ffb0bb040aeb1d18f01821866e5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4cd28ffb0bb040aeb1d18f01821866e5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4cd28ffb0bb040aeb1d18f01821866e5"}}, "title": "Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development.", "authors": [{"family": "Filipek-G\u00f3rniok", "given": "Beata", "initials": "B", "orcid": "0000-0002-6757-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/11f0b7b3e0b045f082d2aff1dd23ec0e.json"}}, {"family": "Holmborn", "given": "Katarina", "initials": "K"}, {"family": "Haitina", "given": "Tatjana", "initials": "T"}, {"family": "Habicher", "given": "Judith", "initials": "J"}, {"family": "Oliveira", "given": "Marta Bastos", "initials": "MB"}, {"family": "Hellgren", "given": "Charlotte", "initials": "C"}, {"family": "Eriksson", "given": "Inger", "initials": "I"}, {"family": "Kjell\u00e9n", "given": "Lena", "initials": "L"}, {"family": "Kreuger", "given": "Johan", "initials": "J"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}], "type": "journal article", "published": "2013-08-00", "journal": {"volume": "242", "issn": "1097-0177", "issue": "8", "pages": "964-975", "title": "Dev. Dyn.", "issn-l": "1058-8388"}, "abstract": "Chondroitin/dermatan sulfate (CS/DS) proteoglycans present in the extracellular matrix have important structural and regulatory functions.\n\nSix human genes have previously been shown to catalyze CS/DS polymerization. Here we show that one of these genes, chpf, is represented by two copies in the zebrafish genome, chpfa and chpfb, while the other five human CS/DS glycosyltransferases csgalnact1, csgalnact2, chpf2, chsy1, and chsy3 all have single zebrafish orthologues. The putative zebrafish CS/DS glycosyltransferases are spatially and temporally expressed. Interestingly, overlapping expression of multiple glycosyltransferases coincides with high CS/DS deposition. Finally, whereas the relative levels of the related polysaccharide HS reach steady-state at around 2 days post fertilization, there is a continued relative increase of the CS amounts per larvae during the first 6 days of development, matching the increased cartilage formation.\n\nThere are 7 CS/DS glycosyltransferases in zebrafish, which, based on homology, can be divided into the CSGALNACT, CHSY, and CHPF families. The overlap between intense CS/DS production and the expression of multiple CS/DS glycosyltransferases suggests that efficient CS/DS biosynthesis requires a combination of several glycosyltransferases.", "doi": "10.1002/dvdy.23981", "pmid": "23703795", "labels": {"Genome Engineering Zebrafish": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:43.737Z", "modified": "2021-07-06T16:05:51.247Z"}, {"entity": "publication", "iuid": "f51ca77cdbe64ad19435f4e55f6cac26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f51ca77cdbe64ad19435f4e55f6cac26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f51ca77cdbe64ad19435f4e55f6cac26"}}, "title": "On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis.", "authors": [{"family": "Holmborn", "given": "Katarina", "initials": "K"}, {"family": "Habicher", "given": "Judith", "initials": "J"}, {"family": "Kasza", "given": "Zsolt", "initials": "Z"}, {"family": "Eriksson", "given": "Anna S", "initials": "AS"}, {"family": "Filipek-Gorniok", "given": "Beata", "initials": "B", "orcid": "0000-0002-6757-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/11f0b7b3e0b045f082d2aff1dd23ec0e.json"}}, {"family": "Gopal", "given": "Sandeep", "initials": "S"}, {"family": "Couchman", "given": "John R", "initials": "JR"}, {"family": "Ahlberg", "given": "Per E", "initials": "PE"}, {"family": "Wiweger", "given": "Malgorzata", "initials": "M"}, {"family": "Spillmann", "given": "Dorothe", "initials": "D"}, {"family": "Kreuger", "given": "Johan", "initials": "J"}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}], "type": "journal article", "published": "2012-09-28", "journal": {"volume": "287", "issn": "1083-351X", "issue": "40", "pages": "33905-33916", "title": "J. Biol. Chem.", "issn-l": "0021-9258"}, "abstract": "The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation of the common proteoglycan linkage tetrasaccharide were analyzed along with ext2 and extl3 mutants, predicted to have defective HS polymerization. Notably, the effects on HS and CS biosynthesis in the respective mutant strains were shown to differ from what had been hypothesized. In uxs1 and b3gat3 mutant larvae, biosynthesis of CS was shown to be virtually abolished, whereas these mutants still were capable of synthesizing 50% of the HS produced in control larvae. extl3 and ext2 mutants on the other hand were shown to synthesize reduced amounts of hypersulfated HS. Further, extl3 mutants produced higher levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies in the single mutant strains, as well as in ext2;uxs1 double mutants, was conducted. A correlation between HS and CS production and phenotypes was found, such that impaired HS biosynthesis was shown to affect chondrocyte intercalation, whereas impaired CS biosynthesis inhibited formation of the extracellular matrix surrounding chondrocytes.", "doi": "10.1074/jbc.M112.401646", "pmid": "22869369", "labels": {"Genome Engineering Zebrafish": null}, "xrefs": [{"db": "pii", "key": "S0021-9258(20)62888-5"}, {"db": "pmc", "key": "PMC3460485"}], "notes": [], "created": "2017-05-04T15:03:43.219Z", "modified": "2021-07-06T16:05:51.263Z"}]}