Phenotypes Associated with This Genotype

Genotype
MGI:3583907

• Allelic Composition: Ins2^Akita/Ins2⁺
• Genetic Background: C57BL/6-Ins2^Akita/J

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

homeostasis/metabolism

hyperglycemia ( J:76224 , J:99412 )

• heterozygous males and females are hyperglycemic by 6 weeks of age (plasma glucose - 325 mg/dL); at 12 and 18 weeks of age, plasma glucose levels in males have appproximately doubled (645 mg/dL and 666 mg/dL) while levels in female mutants have increased much less (341 and 298 mg/dL respectively) (J:76224)

decreased circulating insulin level ( J:321591 )

• mice show decreased glucose-induced plasma insulin levels during glucose tolerance testing

increased energy expenditure ( J:321591 )

• mice exhibit increased energy expenditure in the dark photo-period at 2 to 3 months of age

decreased respiratory quotient ( J:321591 )

• mice present reduced respiratory quotient values at 2 to 3 months of age

impaired glucose tolerance ( J:321591 )

• mice exhibit increased blood glucose levels after glucose injection in glucose tolerance tests

• treatment with a pepducin based on Or12d17 sequence, o109-i2-2, significantly ameliorates the glucose metabolism disorder seen in mutants

increased insulin sensitivity ( J:76224 )

• diabetic males that are hyperglycemic (plasma glucose - ~660 mg/dL) at 12 weeks show a return to euglycemia one hour after receiving 1 unit of insulin, demonstrating insulin sensitivity

immune system

increased leukocyte cell number ( J:99412 )

• after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased

abnormal microglial cell morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

abnormal response to transplant ( J:76224 )

• hyperglycemic male mice transplanted with pancreatic islets from wild-type B6 males become euglycemic in one week after transplant and remain euglycemic until removal of the graft (8 weeks); male mice receiving an allogeneic transplant of BALB/c wild-type islets initially become euglycemic but revert to hyperglycemia because of rejection of the graft

cardiovascular system

abnormal retina vasculature morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina

increased vascular permeability ( J:99412 )

• vascular permeability is increased in the retina

growth/size/body

decreased body weight ( J:99412 , J:321591 )

• at death heterozygous males weigh significantly less than wild-type males (J:99412)

• body weight is decreased at 2 to 3 months of age (J:321591)

nervous system

abnormal microglial cell morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

abnormal astrocyte morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, astrocytes close to large caliber superficial blood vessels in the retina have short projections that do not conjoin with the vessel

vision/eye

abnormal retina vasculature morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina

increased retina apoptosis ( J:99412 )

• after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen

abnormal retina neuronal layer morphology ( J:99412 )

• after 22 weeks of hyperglycemia, in the peripheral regions the inner nuclear layer and inner plexiform layer thickness are reduced by 15.6% and 27%, respectively, and in the central region the thickness of the inner plexiform layer is reduced by 16.7%

abnormal retina ganglion layer morphology ( J:99412 )

• after 22 weeks of hyperglycemia, the number of nuclei in the retinal ganglion cell layer is reduced by 23.4%

hematopoietic system

increased leukocyte cell number ( J:99412 )

• after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased

abnormal microglial cell morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

cellular

increased retina apoptosis ( J:99412 )

• after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:321591 )

• mice exhibit a large reduction in insulin content of islets

• population of CD11c+ macrophages in islets is increased by about 3-fold compared to wild-type mice

decreased pancreatic beta cell number ( J:321591 )

• marker analysis indicates that mice show reduced pancreatic beta cells in islets

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young		DOID:0050524	OMIM:606391	J:99412