J:72981

A locus associated with failure of renal development, Fubi1 (failure of ureteric bud invasion 1), was mapped to mouse Chromosome 2 at approximately 65 cM. 39 (NFS/N x DDY/Stm)F1 x DDY/Stm backcross animals were screened for 52 markers with 75% coverage of the genome in the linkage analysis. Parental DDY/Stm is a substrain of DDY that exhibits renal agenesis in a recessively inherited manner with low penetrance. Parental strain NFS/N is wild type and does not exhibit any renal anomalies. The Fubi1 locus reaches a maximum chi-squared value = 16 at D2Mit63 (65.2 cM). Two candidate genes are located in this region, Wt1 and Fmn1. Sequence and expression analysis of Fmn1 did not detect any differences between DDY/Stm and NFS/N parental strains. Reciprocal congenics were created where a 40 cM region centered around Fubi1 from donor DDY/Stm was introgressed onto the genetic background of NFS/N, and vice versa, for 10 generations. Results showed that the DDY.NFS-Fubi1^DDY/Stm congenic did not develop renal abnormalities. Authors conclude Fubi1 is a modifier gene for at least 2 or more loci that contribute to the renal developmental pathway.