Phenotypes Associated with This Genotype

Genotype
MGI:3583687

• Allelic Composition: Gck^tm1Tka/Gck⁺; Irs1^tm1Tka/Irs1^tm1Tka
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA * ICR

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

decreased body weight ( J:38899 )

• these mice exhibit a body weight that is ~70% of that of wild-type mice throughout life

postnatal growth retardation ( J:38899 )

• these mutants display a similar degree of growth retardation as Irs1^tm1Tka homozygous mutant mice

homeostasis/metabolism

increased circulating insulin level ( J:38899 )

• these mutants exhibit higher, although not statistically significant, fasting insulin levels (148% of wild-type levels)

impaired glucose tolerance ( J:38899 )

• at 15 weeks of age, these mutants display a similar degree of glucose intolerance to Gck^tm1Tka heterozygotes

• however, at 30-40 weeks, these mutants exhibit a "diabetic" glucose tolerance i.e. an exacerbated glucose intolerance relative to Gck^tm1Tka heterozygotes of the same genetic background

insulin resistance ( J:38899 )

• these mutants exhibit insulin resistance relative to Gck^tm1Tka heterozygotes of the same genetic background

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:38899 )

• in these mutants, beta-cell mass per pancreas is 216% of wild-type in terms of area

• in contrast, the non-beta (i.e. alpha and delta) cell mass remains unchanged relative to wild-type

pancreatic islet hyperplasia ( J:38899 )

• a portion of pancreatic islets from these mutant mice appear enlarged due to beta-cell hyperplasia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:38899