Mouse Genome Informatics
ht
    Ins2Akita/Ins2+
C57BL/6-Ins2Akita/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
homeostasis/metabolism
• 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)
• 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
• after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased
• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology
• 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
• after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina
• vascular permeability is increased in the retina

growth/size
• at death heterozygous males weigh significantly less than wild-type males

nervous system
• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology
• 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
• after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina
• after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen
• 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%
• after 22 weeks of hyperglycemia, the number of nuclei in the retinal ganglion cell layer is reduced by 23.4%

hematopoietic system
• after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased
• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

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

Mouse Models of Human Disease
OMIM IDRef(s)
Maturity-Onset Diabetes of the Young; MODY 606391 J:99412