Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period.
Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus induces diabetes, but the effects of its homozygosity on the pancreas remain unknown. F2 mice were obtained by F1 (diabetic C57BL6 x normal Mus musculus castaneus) crosses. About 20% of the F2 progeny developed diabetes by 2 wk of age, 50% of the progeny were normal at 2 wk and developed diabetes between 5 and 8 wk of age, and the remaining 30% did not develop diabetes. Quantitative trait locus analysis using blood glucose levels of 118 F2 mice at 2 wk of age and 5-8 wk of age located Mody within 3 cM of D7Mit258. Histopathological investigation revealed hypoplastic islets (approximately 33% of that of wild-type mice) and a lower density of beta cells (approximately 20% of wild-type) with a reciprocal dominance of alpha cells (four times that of wild-type) in Mody homozygotes. Electron microscopic observations revealed a specific decrease in the number of insulin secretory granules and a lower density of beta cells. Ratios of insulin to glucagon contents confirmed specific decreases in insulin content: 0.01 for homozygotes, 0.54 for heterozygotes, and 1.11 for wild-type mice on day 14. These results suggest that Mody is involved in both islet growth and beta cell function.
Kayo
T
T
Department of Hygiene, Akita University School of Medicine, Akita 010, Japan.
Koizumi
A
A
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D005934:Glucagon / Q000032:analysis; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D008126:Lod Score; D051379:Mice; D016688:Mice, Inbred NOD; D008854:Microscopy, Electron; D010179:Pancreas / Q000254:growth & development; D019655:Quantitative Trait, Heritable
D001786:Blood Glucose; D005819:Genetic Markers; D007328:Insulin; D005934:Glucagon