Mouse Genome Informatics
hm1
    Itga1tm1Gdnr/Itga1tm1Gdnr
involves: 129S4/SvJae * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• increased apoptosis 1 week after treatment with adriamycin
• increased foot process effacement 1 day after treatment with adriamycin
• smaller glomeruli and glomerular tuft area
• increased mesangial matrix accumulation
• mesangial expansion 1 day after treatment with adriamycin
• focal mesangiolysis and lesions 1 day after treatment with adriamycin
• increased succeptibility to adriamycin induced kidney damage
• increased glomerular matrix deposition and hyalinosis by 1 week after treatment with adriamycin
• serious interstitial damage and increased apoptosis 1 week after treatment with adriamycin

homeostasis/metabolism
• abnormally increased creatinine levels as a result of adriamycin treatment
• abnormally increased albuminuria as a result of treatment with adriamycin
• increased susceptibility to glomerulopathy in response to adriamycin-induced kidney injury

cellular
• increased apoptosis 1 week after treatment with adriamycin


Mouse Genome Informatics
cx2
    Ins2Akita/Ins2Akita
Itga1tm1Gdnr/Itga1tm1Gdnr

C.Cg-Ins2Akita Itga1tm1Gdnr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 40% of mutants fail to thrive and have to be euthanized before 6 months of age

cardiovascular system
• mice show a a greater decrease in CD31 positive structures in the glomeruli than in single Ins2Akita homozygotes, indicating collapse of the glomerular tufts

growth/size
• decreased body weight at 4 and 6 months of age compared to wild-type mice or single Itgal1tm1Gdnr homozygotes

homeostasis/metabolism
• develop a similar level of hyperglycemia as in single Ins2Akita homozygotes
• 16-fold increase in albumin-to-creatine ratio at 4 months of age

renal/urinary system
• 16-fold increase in albumin-to-creatine ratio at 4 months of age
• glomerular basement membrane thickening is more severe than in single Ins2Akita homozygotes
• increase in glomerular collagen IV deposition at 6 months of age is more abundant than in single Ins2Akita homozygotes
• mice show a a greater decrease in CD31 positive structures in the glomeruli than in single Ins2Akita homozygotes, indicating collapse of the glomerular tufts
• excessive fibrillar collagen deposition in diffuse and nodular mesangial lesions
• increase in mesangial matrix expansion at 4 and 6 months of age is greater than in single Ins2Akita homozygotes
• diffuse and nodular mesangial sclerosis
• small increase in collagen I in the tubulointerstitial compartment of the kidney
• however tubulointerstitial fibrosis is not observed
• glomerular filtration rate is increased at 4 months of age to a similar level as in single Ins2Akita 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
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:198186


Mouse Genome Informatics
cx3
    Col4a3tm1Dec/Col4a3tm1Dec
Itga1tm1Gdnr/Itga1tm1Gdnr

involves: 129S4/SvJae * 129X1/SvJ * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• decreased accumulation of myofibroblasts in kidneys of 7 week old mice compared to mice only homozygous for the collagen deficiency
• infiltration of the kidney tubular interstitium by macrophage is less in 4 week old mice than in mice only homozygous for the collagen deficiency
• attenuated damage to the glomerular basement membrane although damage still present
• slower rate of renal disease progression
• end stage renal failure delayed to 14.5 weeks rather than 8.5 weeks as in mice only homozygous for the collagen deficiency

homeostasis/metabolism
• onset of proteinuria is delayed relative to mice only homozygous for the collagen deficiency

immune system
• infiltration of the kidney tubular interstitium by macrophage is less in 4 week old mice than in mice only homozygous for the collagen deficiency