[Quantitative trait loci analysis for type I collagen deposition in the kidney during urinary protein load]

Although proteinuria is a predictor of renal outcome, it is also an accelerator of disease progression through renal parenchymal damage such as interstitial fibrosis. Therefore, to elucidate the genetic components contributing to collagen deposition by proteinuria, we employed a strategy to map genetic loci that influence the phenotype in mice that present high or low type I collagen (COLI) deposition in the kidney during proteinuria. Such COLI deposition in 129S1/svImJ and C57BL/6J inbred mouse strains differs most significantly among 9 tested inbred strains. We conducted a quantitative trait loci (QTL) analysis of 120 (129S1/svImJ x C57BL/6J) F1 x 129S1/svImJ backcross mice loaded with bovine serum albumin for 6 weeks to yield proteinuria and cause renal parenchymal damage. COLI deposition in the kidney during proteinuria was influenced by one suggestive QTL (logarithm of odds 2.84) that accounted for 10.2% of the total variance, and its peak position was located at 81.7 cM near D2Mit224 on Chr 2. Progenies with a homologous 129S1/svImJ allele showed more COLI deposition in the kidney than those with heterozygous alleles, suggesting that the 129S1/svIlmJ allele is recessive. Although further studies elucidating candidate genes underlying this region are necessary, such information will provide a chance to unravel the genetics of renal fibrogenesis.