Genotypic and phenotypic characterization of six new recombinant congenic strains derived from NOD/Shi and CBA/J genomes

Recombinant Congenic Strains (RCS) are useful for dissecting complex polyge nic traits. Here, we describe genetic and phenotypic characterization of si x new RCS generated from outcrosses between NOD/Shi and CBA/LsLt, followed by sib mating of first backcross progeny (to CBA) for 20 generations, where upon genetic and phenotypic analysis commenced. Four of the RCS were select ed on the basis of residual heterozygosity present at F20 in one of the thr ee original RCS. Contrary to expectations for RCS developed at first backcr oss, all derived at least 50% of the polymorphic markers typed from the NOD parental strain. Development of autoimmune insulin-dependent diabetes mell itus (IDDM) in NOD is a strain-specific characteristic. The major genetic c omponent predisposing NOD mice to IDDM, their H2(g7) haplotype, was present in all RCS. Nevertheless, the presence of variable amounts of CBA genome a t non-MHC loci conferred complete resistance in all RCS to spontaneous IDDM development, and rendered them strongly res ist ant to cyclophosphamide-in duced IDDM. Although the RCS more resemble NOD in regard to certain strain- specific characteristics, such as prolificacy, an immunologic phenotype tha t was significantly reduced when compared to both parental strains was the number of peripheral CD8(+) T cells. Given the genetic characterization pre sented, these new RCS should prove valuable to investigators interested in studying genes controlling differential susceptibilities distinguishing the NOD and CBA inbred strain backgrounds.