Journal Article

“Agouti NOD”: identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells

Schott, William H., Nagy, Andras, Dosch, Michael H., Scheuplein, Felix, Mileikovsky, Maria, Reifsnyder, Peter C., Soodeen-Karamath, Sharon, Ellis, James, Koch-Nolte, Friedrich, Chen, Jing, Leiter, Edward H.

2005

Overview

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/Tyr(c) 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 (Gpi1(b)) 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.

• Publisher: Springer Nature B.V
• Subject: Animals / Animals, Congenic / Cell Line / Chimera - genetics / Chromosome Mapping / Chromosomes, Mammalian / Diabetes / Diabetes Mellitus, Experimental - blood / Diabetes Mellitus, Experimental - genetics / Embryo, Mammalian - cytology / Female / Insulin - blood / Male / Mice / Mice, Inbred NOD - genetics / Penetrance / Stem Cells