Use of recombinant congenic and congenic strains of NOD mice to identify a new insulin-dependent diabetes resistance gene.
Insulin-dependent diabetes mellitus (IDDM) in NOD/Lt mice represents a complex polygenic disease. NOR/Lt is a recombinant congenic strain (RCS) in which limited regions of the NOD/Lt genome have been replaced by genome from the C57BL/KsJ strain. NOR mice are insulitis resistant and diabetes free despite genetic identity with NOD at numerous chromosomal regions containing previously described insulin-dependent diabetes (Idd) genes, including the strongly diabetogenic H2g7 major histocompatibility complex (MHC) haplotype. The present study revealed BKs-derived genome on segments of chromosomes (Chr) 1, 2, 4, 5, 7, 11, 12, and 18, approximating 11.6% of the total NOR genome analyzed. (NOD x NOR)F2 segregation analysis was employed to identify chromosomal regions in NOR containing Idd resistance alleles. IDDM developed in 33% (10/30) of F1 females, and 29.3% (36/123) of F2 females aged to 1 yr. A previously unrecognized diabetes resistance locus (designated Idd13r) strongly protective in homozygous state was identified on NOR Chr 2 in linkage with the Il1 alpha structural gene. The existence of this locus was confirmed by construction of a NOD stock congenic for NOR-derived markers on Chr 2. Our analysis shows the utility of RCS and congenic stocks for the identification and isolation of non-MHC genes with strong antidiabetogenic functions.
Serreze
D V
DV
Jackson Laboratory, Bar Harbor, Maine 04609.
Prochazka
M
M
Reifsnyder
P C
PC
Bridgett
M M
MM
Leiter
E H
EH
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics*; D008969:Molecular Sequence Data; D011995:Recombination, Genetic