Gene Expression analysis of the HIVAN1 Susceptibility Locus in the FVB-HIVAN1CAST congenic strain

Expression profiling comparing healthy kidneys of wild-type FVB mice and wild-type full congenic FVB-HIVAN1CAST mice HIV-1 transgenic mice on the FVB/NJ background (TgFVB) represent a validated model of HIV-associated nephropathy (HIVAN). A major susceptibility locus, HIVAN1, was previously mapped to chromosome 3A1-A3 in a cross between TgFVB and CAST/EiJ (CAST) strains, and introgression of a 51.9 Mb segment encompassing HIVAN1 from CAST into TgFVB results in accelerated development of nephropathy. We performed genome-wide expression profiling of whole kidneys from wild-type (without the HIV-1 transgene) full congenic FVB-HIVAN1CAST and FVB mouse strains, with the goal of identifying genes with differential renal expression in the HIVAN1 locus that may be associated with the development of nephropathy upon exposure to HIV-1. We only profiled healthy wild-type kidneys because the profound histopathological lesions of HIV-1 transgenic mice introduce many secondary gene expression changes that can confound interpretation of transcriptomic data. We performed microarray analysis with the Affymetrix ST 1.0 gene arrays on kidney RNA from 20 FVB-HIVAN1CAST congenic mice (11 females / 9 males) and 19 FVBN/J littermates (10 females / 9 males). Sample preparation, labeling and hybridization were performed as per Affymetrix recommended protocol. Signal intensities were normalized using the RMA method.