COL4A6 is dispensable for autosomal recessive Alport syndrome

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Murata , T , Katayama , K , Oohashi , T , Jahnukainen , T , Yonezawa , T , Sado , Y , Ishikawa , E , Nomura , S , Tryggvason , K & Ito , M 2016 , ' COL4A6 is dispensable for autosomal recessive Alport syndrome ' , Scientific Reports , vol. 6 , 29450 . https://doi.org/10.1038/srep29450

Title: COL4A6 is dispensable for autosomal recessive Alport syndrome
Author: Murata, Tomohiro; Katayama, Kan; Oohashi, Toshitaka; Jahnukainen, Timo; Yonezawa, Tomoko; Sado, Yoshikazu; Ishikawa, Eiji; Nomura, Shinsuke; Tryggvason, Karl; Ito, Masaaki
Contributor: University of Helsinki, Children's Hospital
Date: 2016-07-05
Language: eng
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/165051
Abstract: Alport syndrome is caused by mutations in the genes encoding alpha 3, alpha 4, or alpha 5 (IV) chains. Unlike X-linked Alport mice, alpha 5 and alpha 6 (IV) chains are detected in the glomerular basement membrane of autosomal recessive Alport mice, however, the significance of this finding remains to be investigated. We therefore generated mice lacking both alpha 3 and alpha 6 (IV) chains and compared their renal function and survival with Col4a3 knockout mice of 129 x 1/Sv background. No significant difference was observed in the renal function or survival of the two groups, or when the mice were backcrossed once to C57BL/6 background. However, the survival of backcrossed double knockout mice was significantly longer than that of the mice of 129 x 1/Sv background, which suggests that other modifier genes were involved in this phenomenon. In further studies we identified two Alport patients who had a homozygous mutation in intron 46 of COL4A4. The alpha 5 and alpha 6 (IV) chains were focally detected in the glomerular basement membrane of these patients. These findings indicate that although a5 and a6 (IV) chains are induced in the glomerular basement membrane in autosomal recessive Alport syndrome, their induction does not seem to play a major compensatory role.
Subject: GLOMERULAR-BASEMENT-MEMBRANE
IV COLLAGEN
MOUSE MODEL
RENAL FIBROSIS
PROLONGS SURVIVAL
ALPHA-CHAINS
MICE
NETWORK
INHIBITOR
GENES
3123 Gynaecology and paediatrics
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