Phenotypes associated with this allele

• Allele Symbol: Itga1^tm1Gdnr
• Allele Name: targeted mutation 1, Humphrey Gardner
• Allele ID: MGI:2451067
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Itga1^tm1Gdnr/Itga1^tm1Gdnr	involves: 129S4/SvJae * BALB/c	MGI:2451068
cx2	Ins2^Akita/Ins2^Akita Itga1^tm1Gdnr/Itga1^tm1Gdnr	C.Cg-Ins2^Akita Itga1^tm1Gdnr	MGI:5508896
cx3	Col4a3^tm1Dec/Col4a3^tm1Dec Itga1^tm1Gdnr/Itga1^tm1Gdnr	involves: 129S4/SvJae * 129X1/SvJ * BALB/c	MGI:3583734

Genotype
MGI:2451068

hm1

• Allelic Composition: Itga1^tm1Gdnr/Itga1^tm1Gdnr
• Genetic Background: involves: 129S4/SvJae * BALB/c

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

renal/urinary system

increased renal glomerulus apoptosis ( J:91522 )

• increased apoptosis 1 week after treatment with adriamycin

podocyte foot process effacement ( J:91522 )

• increased foot process effacement 1 day after treatment with adriamycin

abnormal renal glomerulus morphology ( J:91522 )

• smaller glomeruli and glomerular tuft area

expanded mesangial matrix ( J:91522 )

• increased mesangial matrix accumulation

• mesangial expansion 1 day after treatment with adriamycin

mesangiolysis ( J:91522 )

• focal mesangiolysis and lesions 1 day after treatment with adriamycin

glomerulosclerosis ( J:91522 )

• 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

increased circulating creatinine level ( J:91522 )

• abnormally increased creatinine levels as a result of adriamycin treatment

increased circulating serum albumin level ( J:91522 )

• abnormally increased albuminuria as a result of treatment with adriamycin

increased susceptibility to injury ( J:91522 )

• increased susceptibility to glomerulopathy in response to adriamycin-induced kidney injury

cellular

increased renal glomerulus apoptosis ( J:91522 )

• increased apoptosis 1 week after treatment with adriamycin

Genotype
MGI:5508896

cx2

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

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

Genotype
MGI:3583734

cx3

• Allelic Composition: Col4a3^tm1Dec/Col4a3^tm1Dec; Itga1^tm1Gdnr/Itga1^tm1Gdnr
• Genetic Background: involves: 129S4/SvJae * 129X1/SvJ * BALB/c

renal/urinary system

abnormal kidney morphology ( J:71378 )

• decreased accumulation of myofibroblasts in kidneys of 7 week old mice compared to mice only homozygous for the collagen deficiency

tubular nephritis ( J:71378 )

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

abnormal renal glomerulus basement membrane morphology ( J:91620 )

• attenuated damage to the glomerular basement membrane although damage still present

kidney failure ( J:91620 )

• 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

increased circulating total protein level ( J:91620 )

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

immune system

tubular nephritis ( J:71378 )

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