論文

査読有り
2014年6月

Quantitative Trait Loci for Resistance to the Congenital Nephropathy in Tensin 2-Deficient Mice

PLOS ONE
  • Hayato Sasaki
  • ,
  • Nobuya Sasaki
  • ,
  • Tomohiro Nishino
  • ,
  • Ken-ichi Nagasaki
  • ,
  • Hiroshi Kitamura
  • ,
  • Daisuke Torigoe
  • ,
  • Takashi Agui

9
6
開始ページ
e99602
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0099602
出版者・発行元
PUBLIC LIBRARY SCIENCE

The ICR-derived glomerulonephritis (ICGN) mouse is a chronic kidney disease (CKD) model that is characterized histologically by glomerulosclerosis, vascular sclerosis and tubulointerstitial fibrosis, and clinically by proteinuria and anemia, which are common symptoms and pathological changes associated with a variety of kidney diseases. Previously, we performed a quantitative trait locus (QTL) analysis to identify the causative genes for proteinuria in ICGN mice, and found a deletion mutation of the tensin 2 gene (Tns2(nph), MGI no: 2447990). Interestingly, the congenic strain carrying the Tns2(nph) mutation on a C57BL/6J (B6) genetic background exhibited milder phenotypes than did ICGN mice, indicating the presence of several modifier genes controlling the disease phenotype. In this study, to identify the modifier/resistant loci for CKD progression in Tns2-deficient mice, we performed QTL analysis using backcross progenies from susceptible ICGN and resistant B6 mice. We identified a significant locus on chromosome (Chr) 2 (LOD = 5.36; 31 cM) and two suggestive loci on Chrs 10 (LOD = 2.27; 64 cM) and X (LOD = 2.65; 67 cM) with linkage to the severity of tubulointerstitial injury. One significant locus on Chr 13 (LOD = 3.49; approximately 14 cM) and one suggestive locus on Chr 2 (LOD = 2.41; 51 cM) were identified as QTLs for the severity of glomerulosclerosis. Suggestive locus in BUN was also detected in the same Chr 2 region (LOD = 2.34; 51 cM). A locus on Chr 2 (36 cM) was significantly linked with HGB (LOD = 4.47) and HCT (LOD = 3.58). Four novel epistatic loci controlling either HGB or tubulointerstitial injury were discovered. Further genetic analysis should lead to identification of CKD modifier gene(s), aiding early diagnosis and providing novel approaches to the discovery of drugs for the treatment and possible prevention of kidney disease.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0099602
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24967628
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000338280800015&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0099602
  • ISSN : 1932-6203
  • PubMed ID : 24967628
  • Web of Science ID : WOS:000338280800015

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