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Congenital nephrotic syndrome of the Finnish type (CNF) (MIM# 256300) is caused by biallelic variants in the gene <jats:italic>NPHS1<\/jats:italic>, encoding nephrin, an integral component of the kidney filtration barrier. No causal treatments exist, and children inevitably require kidney replacement therapy. In preparation for gene replacement therapy (GRT) in CNF, we established a quantifiable and reproducible phenotypic assessment of the nephrin-deficient CNF mouse model: 129\/Sv-<jats:italic>Nphs1<\/jats:italic><jats:sup><jats:italic>tm1Rkl<\/jats:italic><\/jats:sup><jats:italic>\/J<\/jats:italic>. We assessed the phenotypic spectrum of homozygous mice (<jats:italic>Nphs1<\/jats:italic><jats:sup><jats:italic>tm1Rkl<\/jats:italic><\/jats:sup><jats:italic>\/Nphs1<\/jats:italic><jats:sup><jats:italic>tm1Rkl<\/jats:italic><\/jats:sup>) compared to heterozygous controls (<jats:italic>Nphs1<\/jats:italic><jats:sup><jats:italic>tm1Rkl<\/jats:italic><\/jats:sup><jats:italic>\/Nphs1<\/jats:italic><jats:sup><jats:italic>WT<\/jats:italic><\/jats:sup>) by the following parameters: 1. cohort survival, 2. podocyte foot process (FP) density per glomerular basement membrane (GBM) using transmission electron microscopy, 3. tubular microcysts in brightfield microscopy, and 4. urinary albumin\/creatinine ratios. <jats:italic>Nphs1<\/jats:italic><jats:sup><jats:italic>tm1Rkl<\/jats:italic><\/jats:sup><jats:italic>\/Nphs1<\/jats:italic><jats:sup><jats:italic>tm1Rkl<\/jats:italic><\/jats:sup> mice exhibited: 1. perinatal lethality with median survival of 1\u00a0day, 2. FP effacement with median FP density of 1.00 FP\/\u00b5m GBM (2.12 FP\/\u00b5m in controls), 3. tubular dilation with 65 microcysts per section\u00a0(6.5 in controls), and 4. increased albumin\/creatinine ratio of 238\u00a0g\/g (4.1\u00a0g\/g in controls). We here established four quantifiable phenotyping features of a CNF mouse model to facilitate future GRT studies by enabling sensitive detection of phenotypic improvements.<\/jats:p>","DOI":"10.1038\/s41598-024-64883-y","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T08:02:35Z","timestamp":1720598555000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantifiable and reproducible phenotypic assessment of a constitutive knockout mouse model for congenital nephrotic syndrome of the Finnish type"],"prefix":"10.1038","volume":"14","author":[{"given":"Katharina","family":"Lemberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils D.","family":"Mertens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirollos","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronen","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea M.","family":"Merz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bshara","family":"Mansour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daanya","family":"Salmanullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline M.","family":"Kolvenbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Saida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyoung","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selina","family":"H\u00f6lzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Steinsapir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin A.","family":"Goncalves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Nicolas Frank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gijs A. 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