Accelerated development of collapsing glomerulopathy in mice congenic for the HIVAN1 locus

Ka T. Chan, Natalia Papeta, Jeremiah Martino, Zongyu Zheng, Rachelle Z. Frankel, Paul E. Klotman, Vivette D. D'Agati, Richard P. Lifton, Ali G. Gharavi

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

HIV-1 transgenic mice on the FVB/NJ background (TgFVB) are a well validated model of HIV-associated nephropathy (HIVAN). A mapping study between TgFVB and CAST/EiJ (CAST) strains showed this trait to be influenced by a major susceptibility locus on chromosome 3A1-A3 (HIVAN1), with CAST alleles associated with increased risk of disease. We introgressed a 50 Mb interval, encompassing this HIVAN1 locus, from CAST into the TgFVB genome (TgFVB-HIVAN1CAST congenic mice). Compared to the TgFVB strain, these congenic mice developed an earlier onset of proteinuria, a rapid progression to kidney failure, and increased mortality. A prospective study of these congenic mice also showed that they had a significantly greater histologic and biochemical evidence of glomerulopathy with one-third of mice developing global glomerulosclerosis by 6 weeks of age. An F2 cross between TgFVB and the congenic mice identified a significant linkage (LOD = 3.7) to a 10 cM interval within the HIVAN1 region between D3Mit167 and D3Mit67 resulting in a 60% reduction of the original interval. These data independently confirm that a gene on chromosome 3A1-A3 increases susceptibility to HIVAN, resulting in early onset and rapid progression of kidney disease. These mice represent a new model to study the development and progression of collapsing glomerulopathy.

Original languageEnglish
Pages (from-to)366-372
Number of pages7
JournalKidney International
Volume75
Issue number4
DOIs
StatePublished - Feb 2009
Externally publishedYes

Keywords

  • Genetic susceptibility
  • HIV-associated nephropathy
  • Mouse model

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