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By 14 weeks, half of the glomeruli were fibrotic with collapsed capillaries. Immunofluorescence analysis of the GBM showed the absence of type IV collagen alpha-3, alpha-4, and alpha-5 chains and a persistence of alpha-1 and alpha-2 chains (these chains normally localize to the mesangial matrix). Northern blot analysis using probes specific for the collagen chains illustrate the absence of COL4A3 in the knockout, whereas mRNAs for the remaining chains are unchanged. An accumulation of fibronectin, heparan sulfate proteoglycan, laminin-1, and entactin was observed in the GBM of the affected animals. The temporal and spatial pattern of accumulation was consistent with that for thickening of the GBM as observed by TEM. Thus, expression of these basement membrane-associated proteins may be involved in the progression of Alport renal disease pathogenesis. The levels of mRNAs encoding the basement membrane-associated proteins at 7 weeks were unchanged.<\/jats:p>","DOI":"10.1101\/gad.10.23.2981","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:15:46Z","timestamp":1181078146000},"page":"2981-2992","source":"Crossref","is-referenced-by-count":314,"title":["Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome."],"prefix":"10.1101","volume":"10","author":[{"given":"D","family":"Cosgrove","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D T","family":"Meehan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Grunkemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Kornak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Sayers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W J","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G C","family":"Samuelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1996,12,1]]},"reference":[{"key":"2021111418412878000_10.23.2981.1","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1172\/JCI117073","article-title":"Deletions in the COL4A5 collagen gene in X-linked Alport syndrome.","volume":"93","year":"1994","journal-title":"Am. 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