Abstract
The ICGN mouse strain is a glomerulosclerosis (GS) model that shows characteristic proteinuria, podocytes morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which are the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously we performed a quantitative trait locus (QTL) analysis to identify the causative genes for GS in ICGN mice, and found the deletion mutation of the tensin2 (Tns2) gene that creates both a premature stop codon and dramatically decreases mRNA expression levels within the region of the major QTL (this mutation was designated Tns2nep). The severity of GS varies considerably in humans and other animals, indicating the influence of several genes controlling the disease phenotype. In this study, to identify the modifier/resistant gene(s) to GS, we produced congenic strains carrying the Tns2nep mutation on the C57BL/6J (B6) genetic background and analyzed GS severity. Interestingly, the B6 congenic mice exhibited milder phenotypes than did ICGN strain mice. The results suggest that B6 have modifier(s) of GS resistance. Therefore, the identification of the modifier loci in B6 mice will provide important new information regarding gene interactions controlling GS.
