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Phenotypes Associated with This Genotype
Genotype
MGI:2177705
Allelic
Composition
Gcktm1Tka/Gcktm1Tka
Genetic
Background
involves: 129X1/SvJ * ICR
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gcktm1Tka mutation (0 available); any Gck mutation (26 available)
phenotype observed in females
phenotype observed in males
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 (J:30334)
• administration of human insulin or glibenclamide extends pup survival to greater than 7 days and greater than 10 days of age, respectively (J:30334)
• homozygous mutant pups develop severe diabetes shortly after birth and die by 7 days of age probably due to dehydration (J:30334)
• administration of human insulin or glibenclamide extends pup survival to greater than 7 days and greater than 10 days of age, respectively (J:30334)

growth/size/body
• homozygous pups exhibit normal appearance and size/weight at birth, but no increase in body weight with age (J:30334)
• administration of human insulin or glibenclamide restores gain in body weight to ~80% of wild-type littermates (J:30334)
• homozygous pups exhibit normal appearance and size/weight at birth, but no increase in body weight with age (J:30334)
• administration of human insulin or glibenclamide restores gain in body weight to ~80% of wild-type littermates (J:30334)

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 (J:30334)
• 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 (J:30334)
• at 3-4 days of age, homozygotes display significantly higher blood glucose levels than wild-type or heterozygous littermates (J:30334)
• administration of human insulin or glibenclamide lowers blood glucose levels by 20-40% (J:30334)
• at 3-4 days of age, homozygotes display significantly higher blood glucose levels than wild-type or heterozygous littermates (J:30334)
• administration of human insulin or glibenclamide lowers blood glucose levels by 20-40% (J:30334)
• at 3-4 days of age, homozygotes display low serum insulin levels relative to the elevated blood glucose levels (J:30334)
• at 3-4 days of age, homozygotes display low serum insulin levels relative to the elevated blood glucose levels (J:30334)
• only 20% of homozygotes exhibit ketosis in spite of marked hyperglycemia, suggesting that basal insulin secretion is preserved (J:30334)
• only 20% of homozygotes exhibit ketosis in spite of marked hyperglycemia, suggesting that basal insulin secretion is preserved (J:30334)
• homozygotes display significant glycosuria within a day after birth (J:30334)
• homozygotes display significant glycosuria within a day after birth (J:30334)

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)
• 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 (J:30334)
• in these islets, the rise in intracellular calcium elicited by glucose and glibenclamide is completely abolished whereas that by arginine is modestly impaired (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 (J:30334)
• in these islets, the rise in intracellular calcium elicited by glucose and glibenclamide is completely abolished whereas that by arginine is modestly impaired (J:30334)
• 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 (J:30334)
• 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 (J:30334)

renal/urinary system
• homozygotes display significant glycosuria within a day after birth (J:30334)
• homozygotes display significant glycosuria within a day after birth (J:30334)

liver/biliary system
• homozygotes display occasional fatty changes in the liver; other organs appear grossly normal (J:30334)
• homozygotes display occasional fatty changes in the liver; other organs appear grossly normal (J:30334)

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


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
02/02/2016
MGI 6.02
The Jackson Laboratory