Penetrance of the complex of genes predisposing the nonobese diabetic (NOD) mouse to autoimmune diabetes is affected by the
maternal environment. NOD.CBALs-
Tyr+/Lt is an agouti-pigmented Chromosome 7 congenic stock of NOD/Lt mice produced as a resource for embryo transfer experiments
to provide the necessary maternal factors and allow the easy identification of NOD (albino) embryo donor phenotype. CBcNO6/Lt,
a recombinant congenic agouti stock already containing approximately 50% NOD genome, was used as the donor source of a wild-type
CBA tyrosinase allele. When the incidence of diabetes was assessed after nine generations of backcrossing and one generation
of sib-sib mating, significant reduction in diabetes development was observed. No difference in diabetes development was observed
in
Tyr/Tyrc heterozygotes, showing that protection was recessive. Analysis of diabetes progression in another NOD stock congenic for
C57BL/6 alleles on Chromosome 7 linked to the glucose phosphate isomerase (
Gpi1b) locus provided no protection, indicating that the diabetes resistance (
Idd) gene was distal to 34 cM (
D7Mit346). Approximately 5 cM of the distal congenic region overlaps a region from C57L previously associated with protection when
homozygous. The delayed onset and reduced frequency of diabetes in the NOD.CBALs-
Tyr+/Lt stock is an advantage when females of this stock are used as surrogate mothers in studies involving hysterectomy or embryo
transfers. Indeed, a newly developed NOD embryonic stem (ES) cell line injected into NOD.CBALs-
Tyr+/Lt blastocysts produced approximately 50% live-born mice, of which approximately 11% were chimeric. Presumably because of
high genomic instability, no germline transmission was observed.