Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice.
Insulin-dependent diabetes mellitus (IDDM) is a polygenic disease caused by autoimmune destruction of insulin-producing beta cells in the islets of Langerhans. Its onset is preceded by a long and variable period in which lymphoid cells infiltrate the pancreas but first remain outside the islets (peri-insulitis) before invading them (insulitis). Among susceptibility loci, only the major histocompatibility complex (MHC) has been clearly assigned. Genetic study of the nonobese diabetic (NOD) mouse model for insulin-dependent diabetes mellitus has revealed genetic linkage of insulitis and of early onset diabetes with two non-MHC loci mapping to chromosome 3 and 11 respectively. Here we report a close association of periinsulitis with a third non-MHC locus mapping to chromosome 1. Successive stages in the progression of diabetic disease thus appear to be controlled by distinct genes or sets of genes.
Garchon
H J
HJ
INSERM U 25, Hôpital Necker, Pairs, France.
Bedossa
P
P
Eloy
L
L
Bach
J F
JF
D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010182:Pancreatic Diseases / Q000235:genetics* / Q000473:pathology; D012466:Salivary Gland Diseases / Q000235:genetics / Q000473:pathology