Mouse Genome Informatics
hm
    Gcktm1Tka/Gcktm1Tka
involves: 129X1/SvJ * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygous mutant pups develop severe diabetes shortly after birth and die by 7 days of age probably due to dehydration
• administration of human insulin or glibenclamide extends pup survival to greater than 7 days and greater than 10 days of age, respectively

growth/size
• homozygous pups exhibit normal appearance and size/weight at birth, but no increase in body weight with age
• administration of human insulin or glibenclamide restores gain in body weight to ~80% of wild-type littermates

homeostasis/metabolism
• homozygous islets display no increase in insulin secretion in response to 20 mM glucose, normal insulin secretion in response to arginine, and a 50-80% decrease in insulin secretion in response to glibenclamide
• at 3-4 days of age, homozygotes display significantly higher blood glucose levels than wild-type or heterozygous littermates
• administration of human insulin or glibenclamide lowers blood glucose levels by 20-40%
• at 3-4 days of age, homozygotes display low serum insulin levels relative to the elevated blood glucose levels
• only 20% of homozygotes exhibit ketosis in spite of marked hyperglycemia, suggesting that basal insulin secretion is preserved
• homozygotes display significant glycosuria within a day after birth

endocrine/exocrine glands
N
• homozygotes display relatively normal development and differentiation of endocrine pancreas, with normal islet insulin content and only subtle changes in alpha, beta, and delta cell architecture (J:30334)
• ~80% of islets isolated from 7-10-day-old homozygotes display higher basal calcium levels (> 200 nM) relative to <10% of wild-type or heterozygous islets
• in these islets, the rise in intracellular calcium elicited by glucose and glibenclamide is completely abolished whereas that by arginine is modestly impaired
• homozygous islets display no increase in insulin secretion in response to 20 mM glucose, normal insulin secretion in response to arginine, and a 50-80% decrease in insulin secretion in response to glibenclamide

renal/urinary system
• homozygotes display significant glycosuria within a day after birth

liver/biliary system
• homozygotes display occasional fatty changes in the liver; other organs appear grossly normal

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:30334