{"entity": "researcher", "timestamp": "2026-07-19T18:19:45.870Z", "family": "H\u00f6hne", "given": "Martin", "initials": "M", "orcid": "0000-0001-8698-5389", "affiliations": ["Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/4d3ddd0be3164d0d9f483d9c0755c499.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/4d3ddd0be3164d0d9f483d9c0755c499"}}, "publications": [{"entity": "publication", "iuid": "5dccd398fcd043f78dc23e8efdfe16c2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5dccd398fcd043f78dc23e8efdfe16c2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5dccd398fcd043f78dc23e8efdfe16c2"}}, "title": "Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular Disease.", "authors": [{"family": "Butt", "given": "Linus", "initials": "L"}, {"family": "Unnersj\u00f6-Jess", "given": "David", "initials": "D"}, {"family": "H\u00f6hne", "given": "Martin", "initials": "M", "orcid": "0000-0001-8698-5389", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d3ddd0be3164d0d9f483d9c0755c499.json"}}, {"family": "Hahnfeldt", "given": "Robert", "initials": "R"}, {"family": "Reilly", "given": "Dervla", "initials": "D"}, {"family": "Rinschen", "given": "Markus M", "initials": "MM"}, {"family": "Plagmann", "given": "Ingo", "initials": "I", "orcid": "0000-0003-0263-7040", "researcher": {"href": "https://publications.scilifelab.se/researcher/ffed346895164db69951f6d62b2eaad6.json"}}, {"family": "Diefenhardt", "given": "Paul", "initials": "P"}, {"family": "Br\u00e4hler", "given": "Sebastian", "initials": "S"}, {"family": "Brinkk\u00f6tter", "given": "Paul T", "initials": "PT"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Blom", "given": "Hans", "initials": "H"}, {"family": "Schermer", "given": "Bernhard", "initials": "B"}, {"family": "Benzing", "given": "Thomas", "initials": "T"}], "type": "journal article", "published": "2022-01-00", "journal": {"title": "J. Am. Soc. Nephrol.", "issn": "1533-3450", "pages": "138-154", "volume": "33", "issue": "1", "issn-l": "1046-6673"}, "abstract": "Diseases of the kidney's glomerular filtration barrier are a leading cause of end stage renal failure. Despite a growing understanding of genes involved in glomerular disorders in children, the vast majority of adult patients lack a clear genetic diagnosis. The protein podocin p.R229Q, which results from the most common missense variant in NPHS2, is enriched in cohorts of patients with FSGS. However, p.R229Q has been proposed to cause disease only when transassociated with specific additional genetic alterations, and population-based epidemiologic studies on its association with albuminuria yielded ambiguous results.\n\nTo test whether podocin p.R229Q may also predispose to the complex disease pathogenesis in adults, we introduced the exact genetic alteration in mice using CRISPR/Cas9-based genome editing (Pod ). We assessed the phenotype using super-resolution microscopy and albuminuria measurements and evaluated the stability of the mutant protein in cell culture experiments.R231Q\n\nHeterozygous Pod mice did not present any overt kidney disease or proteinuria. However, homozygous R231Q/wild-typePod mice developed increased levels of albuminuria with age, and super-resolution microscopy revealed preceding ultrastructural morphologic alterations that were recently linked to disease predisposition. When injected with nephrotoxic serum to induce glomerular injury, heterozygous R231Q/R231QPod mice showed a more severe course of disease compared with R231Q/wild-typePod mice. Podocin protein levels were decreased in wild-type/wild-typePod and R231Q/wild-typePod mice as well as in human cultured podocytes expressing the podocinR231Q/R231QR231Q variant. Our in vitro experiments indicate an underlying increased proteasomal degradation.\n\nOur findings demonstrate that podocin R231Q exerts a pathogenic effect on its own, supporting the concept of podocin R229Q contributing to genetic predisposition in adult patients.", "doi": "10.1681/ASN.2020060858", "pmid": "34853150", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ASN.2020060858"}], "notes": [], "created": "2021-12-09T11:32:19.722Z", "modified": "2022-01-03T10:03:04.921Z"}, {"entity": "publication", "iuid": "ccaa6b6173b94902bf80b8a831521a1a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ccaa6b6173b94902bf80b8a831521a1a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ccaa6b6173b94902bf80b8a831521a1a"}}, "title": "A molecular mechanism explaining albuminuria in kidney disease.", "authors": [{"family": "Butt", "given": "Linus", "initials": "L"}, {"family": "Unnersj\u00f6-Jess", "given": "David", "initials": "D", "orcid": "0000-0002-4162-0973", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d475fc7a52a46e4abe984191c5b5b5f.json"}}, {"family": "H\u00f6hne", "given": "Martin", "initials": "M", "orcid": "0000-0001-8698-5389", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d3ddd0be3164d0d9f483d9c0755c499.json"}}, {"family": "Edwards", "given": "Aurelie", "initials": "A"}, {"family": "Binz-Lotter", "given": "Julia", "initials": "J", "orcid": "0000-0003-4678-0703", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a5b26232abe4fd6b4df6c1cadc56f1f.json"}}, {"family": "Reilly", "given": "Dervla", "initials": "D"}, {"family": "Hahnfeldt", "given": "Robert", "initials": "R", "orcid": "0000-0001-7997-3216", "researcher": {"href": "https://publications.scilifelab.se/researcher/e54b718629e742cf966ea885a9120ef5.json"}}, {"family": "Ziegler", "given": "Vera", "initials": "V"}, {"family": "Fremter", "given": "Katharina", "initials": "K"}, {"family": "Rinschen", "given": "Markus M", "initials": "MM", "orcid": "0000-0002-9252-1342", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b6fcd4a72d346cf865aed8b10f49a2d.json"}}, {"family": "Helmst\u00e4dter", "given": "Martin", "initials": "M"}, {"family": "Ebert", "given": "Lena K", "initials": "LK"}, {"family": "Castrop", "given": "Hayo", "initials": "H"}, {"family": "Hackl", "given": "Matthias J", "initials": "MJ"}, {"family": "Walz", "given": "Gerd", "initials": "G", "orcid": "0000-0002-4950-9946", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9545e1cff9413e9c2b76920aa53b3e.json"}}, {"family": "Brinkkoetter", "given": "Paul T", "initials": "PT"}, {"family": "Liebau", "given": "Max C", "initials": "MC", "orcid": "0000-0003-0494-9080", "researcher": {"href": "https://publications.scilifelab.se/researcher/678310bc460e4921bb67c6c6670f24d0.json"}}, {"family": "Tory", "given": "K\u00e1lm\u00e1n", "initials": "K", "orcid": "0000-0002-0316-6212", "researcher": {"href": "https://publications.scilifelab.se/researcher/774101da128248578efdccb22b38475b.json"}}, {"family": "Hoyer", "given": "Peter F", "initials": "PF", "orcid": "0000-0002-9132-0282", "researcher": {"href": "https://publications.scilifelab.se/researcher/b12d4092ef9347c1ba1e982e535b9819.json"}}, {"family": "Beck", "given": "Bodo B", "initials": "BB"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Schermer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-5194-9000", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6ccc28a64e9402fa608fb657d874080.json"}}, {"family": "Benzing", "given": "Thomas", "initials": "T", "orcid": "0000-0003-0512-1066", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c18d7e8857e426b9e6f38b06cca6992.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "volume": "2", "issue": "5", "pages": "461-474", "issn-l": "2522-5812"}, "abstract": "Mammalian kidneys constantly filter large amounts of liquid, with almost complete retention of albumin and other macromolecules in the plasma. Breakdown of the three-layered renal filtration barrier results in loss of albumin into urine (albuminuria) across the wall of small renal capillaries, and is a leading cause of chronic kidney disease. However, exactly how the renal filter works and why its permeability is altered in kidney diseases is poorly understood. Here we show that the permeability of the renal filter is modulated through compression of the capillary wall. We collect morphometric data prior to and after onset of albuminuria in a mouse model equivalent to a human genetic disease affecting the renal filtration barrier. Combining quantitative analyses with mathematical modelling, we demonstrate that morphological alterations of the glomerular filtration barrier lead to reduced compressive forces that counteract filtration pressure, thereby resulting in capillary dilatation, and ultimately albuminuria. Our results reveal distinct functions of the different layers of the filtration barrier and expand the molecular understanding of defective renal filtration in chronic kidney disease.", "doi": "10.1038/s42255-020-0204-y", "pmid": "32694662", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s42255-020-0204-y"}], "notes": [], "created": "2020-05-26T07:14:25.600Z", "modified": "2021-11-10T12:51:42.052Z"}]}