Phenotypes Associated with This Genotype

Genotype
MGI:3623394

• Allelic Composition: Hnf1a^tm1.1Ylee/Hnf1a^tm1.1Ylee
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:47008 )

• homozygous mice are born at less than half the expected frequency

growth/size/body

decreased body size ( J:47008 )

• homozygotes are slightly smaller than wild-type or heterozygous littermates

enlarged liver ( J:47008 )

• livers of 5 week old null mice are 50% larger than that of normal littermates; nulls develop central lobular hyperplasia, with degeneration of individual hepatocytes obvious at 12 weeks

homeostasis/metabolism

hyperglycemia ( J:47008 )

• 2 weeks after birth nulls develop hyperglycemia; null mice develop diabetes by 2 weeks of age

decreased circulating insulin level ( J:47008 )

• at 5 and 12 weeks, the circulating insulin levels in null mice are 60% of levels in heterozygotes

decreased circulating insulin-like growth factor I level ( J:47008 )

• levels of insulin-like growth factor I in the blood of null mice are only 20-30% that of control mice

increased circulating growth hormone level ( J:47008 )

• at 5 weeks of age, GH levels in null mice are 100 times and 45 times higher than those in control female and male mice

increased urine glucose level ( J:47008 )

• 6 week old null mice have urine glucose levels 330x higher than heterozygotes

increased cholesterol level ( J:47008 )

• cholesterol levels are higher in nulls than in heterozygotes

behavior/neurological

abnormal sexual interaction ( J:47008 )

♂ • null males show no mating behavior when paired with wild-type or null females

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:47008 )

• the amount of insulin peptide and insulin-secreting cells in null mice are severely reduced

decreased pancreatic beta cell number ( J:47008 )

• the insulin-secreting cells in null mice are severely reduced

reproductive system

abnormal reproductive system morphology ( J:47008 )

• reproductive organs in both sexes are underdeveloped in null animals

abnormal spermatogenesis ( J:47008 )

♂ • null males have significantly reduced spermatogenesis

infertility ( J:47008 )

• null mice of both sexes are infertile

renal/urinary system

increased urine glucose level ( J:47008 )

• 6 week old null mice have urine glucose levels 330x higher than heterozygotes

polyuria ( J:47008 )

• null mice urinate more frequently than normal mice and diuresis is twice the control level

liver/biliary system

enlarged liver ( J:47008 )

• livers of 5 week old null mice are 50% larger than that of normal littermates; nulls develop central lobular hyperplasia, with degeneration of individual hepatocytes obvious at 12 weeks

abnormal hepatocyte morphology ( J:47008 )

• hepatocytes from null mice are highly vacuolated and seemed to have an abnormal accumulation of complex carbohydrates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young type 3		DOID:0111102	OMIM:600496	J:47008
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:47008