title: "Agouti NOD": identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells.
abstract: 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.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609-1500, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Peter C
authors.initials: PC
authors.lastname: Reifsnyder
authors.forename: Felix
authors.initials: F
authors.lastname: Scheuplein
authors.forename: William H
authors.initials: WH
authors.lastname: Schott
authors.forename: Maria
authors.initials: M
authors.lastname: Mileikovsky
authors.forename: Sharon
authors.initials: S
authors.lastname: Soodeen-Karamath
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.forename: Michael H
authors.initials: MH
authors.lastname: Dosch
authors.forename: James
authors.initials: J
authors.lastname: Ellis
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
authors.forename: Edward H
authors.initials: EH
authors.lastname: Leiter
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D002460:Cell Line; D002678:Chimera / Q000235:genetics*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics*; D019683:Penetrance; D013234:Stem Cells
chemical_list: D007328:Insulin