Phenotypes Associated with This Genotype

Genotype
MGI:5508896

• Allelic Composition: Ins2^Akita/Ins2^Akita; Itga1^tm1Gdnr/Itga1^tm1Gdnr
• Genetic Background: C.Cg-Ins2^Akita Itga1^tm1Gdnr

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

mortality/aging

premature death ( J:198186 )

• about 40% of mutants fail to thrive and have to be euthanized before 6 months of age

cardiovascular system

abnormal glomerular capillary morphology ( J:198186 )

• mice show a a greater decrease in CD31 positive structures in the glomeruli than in single Ins2^Akita homozygotes, indicating collapse of the glomerular tufts

growth/size/body

decreased body weight ( J:198186 )

• decreased body weight at 4 and 6 months of age compared to wild-type mice or single Itgal1^tm1Gdnr homozygotes

homeostasis/metabolism

hyperglycemia ( J:198186 )

• develop a similar level of hyperglycemia as in single Ins2^Akita homozygotes

albuminuria ( J:198186 )

• 16-fold increase in albumin-to-creatine ratio at 4 months of age

renal/urinary system

abnormal glomerular capillary morphology ( J:198186 )

• mice show a a greater decrease in CD31 positive structures in the glomeruli than in single Ins2^Akita homozygotes, indicating collapse of the glomerular tufts

albuminuria ( J:198186 )

• 16-fold increase in albumin-to-creatine ratio at 4 months of age

increased renal glomerulus basement membrane thickness ( J:198186 )

• glomerular basement membrane thickening is more severe than in single Ins2^Akita homozygotes

abnormal glomerular mesangium morphology ( J:198186 )

• excessive fibrillar collagen deposition in diffuse and nodular mesangial lesions

expanded mesangial matrix ( J:198186 )

• increase in mesangial matrix expansion at 4 and 6 months of age is greater than in single Ins2^Akita homozygotes

• diffuse and nodular mesangial sclerosis

mesangiolysis ( J:198186 )

glomerulosclerosis ( J:198186 )

• severe

renal glomerular protein deposits ( J:198186 )

• increase in glomerular collagen IV deposition at 6 months of age is more abundant than in single Ins2^Akita homozygotes

abnormal kidney interstitium morphology ( J:198186 )

• small increase in collagen I in the tubulointerstitial compartment of the kidney

• however tubulointerstitial fibrosis is not observed

increased renal glomerular filtration rate ( J:198186 )

• glomerular filtration rate is increased at 4 months of age to a similar level as in single Ins2^Akita homozygotes

• by 6 months of age, glomerular filtration rate is decreased compared to controls, with an overall 50% decline compared to at 4 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:198186