Phenotypes associated with this allele

• Allele Symbol: Itgb1^tm1Ross
• Allele Name: targeted mutation 1, Robert S Ross
• Allele ID: MGI:2656179
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Itgb1^tm1Ross/Itgb1^tm1Ross Myl2^tm1(cre)Krc/Myl2^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * Black Swiss	MGI:2656180
cn2	Itgb1^tm1Ross/Itgb1^tm1Ross Tg(Hoxb7-cre)13Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5289691

Genotype
MGI:2656180

cn1

• Allelic Composition: Itgb1^tm1Ross/Itgb1^tm1Ross; Myl2^tm1(cre)Krc/Myl2⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * Black Swiss

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:82534 )

• after 7 days of aortic constriction, only 53% of mutants survive compared to 88% of controls

cardiovascular system

liver vascular congestion ( J:82534 )

• show liver congestion at about 6 months of age

abnormal myocardium layer morphology ( J:82534 )

• myocardium shows focal dissolution of myofibrils and intercalated disks as well as mitochondrial swelling, with disruption and loss of cristae

abnormal myocardial fiber morphology ( J:82534 )

• heart sections show disruption of myocyte cell membrane integrity

increased heart atrium size ( J:82534 )

• enlarged at around 6 months of age

abnormal heart ventricle morphology ( J:82534 )

• calcification within the ventricular wall at about 6 months of age

thick ventricular wall ( J:82534 )

• at 6 months of age

cardiac fibrosis ( J:82534 )

• adults develop patchy fibrosis in the ventricular wall

• hearts show replacement fibrosis at around 6 months of age

dilated heart ( J:82534 )

• dilation at about 6 months of age

dilated heart left ventricle ( J:82534 )

• at 6 months of age

dilated heart right ventricle ( J:82534 )

• at 6 months of age

dilated cardiomyopathy ( J:82534 )

abnormal cardiac muscle cell glucose uptake ( J:82534 )

• display abnormal glucose metabolism in the ventricular tissue with patchy uptake of fluorodeoxyglucose (FDG) throughout the ventricular myocardium

decreased heart left ventricle muscle contractility ( J:82534 )

• contractility of the left ventricle is impaired at 5 weeks of age, however left ventricular end-diastolic pressure and heart rate do not vary from controls

abnormal cardiac muscle relaxation ( J:82534 )

• relaxation of the left ventricle is impaired at 5 weeks of age

increased response of heart to induced stress ( J:82534 )

• hemodynamic loading imposed by 7 days of transverse aortic constriction shows that mutants are intolerant of this stress as they have 53% survival versus 88% in controls

congestive heart failure ( J:82534 )

• show signs of congestive heart failure when reach about 6 months of age, including pleural effusions and liver congestion

homeostasis/metabolism

increased response of heart to induced stress ( J:82534 )

• hemodynamic loading imposed by 7 days of transverse aortic constriction shows that mutants are intolerant of this stress as they have 53% survival versus 88% in controls

abnormal atrial thrombosis ( J:82534 )

• hearts show thrombi in enlarged atria at around 6 months of age

pleural effusion ( J:82534 )

• show pleural effusions at about 6 months of age

liver/biliary system

liver vascular congestion ( J:82534 )

• show liver congestion at about 6 months of age

muscle

abnormal myocardium layer morphology ( J:82534 )

• myocardium shows focal dissolution of myofibrils and intercalated disks as well as mitochondrial swelling, with disruption and loss of cristae

abnormal myocardial fiber morphology ( J:82534 )

• heart sections show disruption of myocyte cell membrane integrity

dilated cardiomyopathy ( J:82534 )

abnormal cardiac muscle cell glucose uptake ( J:82534 )

• display abnormal glucose metabolism in the ventricular tissue with patchy uptake of fluorodeoxyglucose (FDG) throughout the ventricular myocardium

decreased heart left ventricle muscle contractility ( J:82534 )

• contractility of the left ventricle is impaired at 5 weeks of age, however left ventricular end-diastolic pressure and heart rate do not vary from controls

abnormal cardiac muscle relaxation ( J:82534 )

• relaxation of the left ventricle is impaired at 5 weeks of age

respiratory system

pleural effusion ( J:82534 )

• show pleural effusions at about 6 months of age

cellular

abnormal cardiac muscle cell glucose uptake ( J:82534 )

• display abnormal glucose metabolism in the ventricular tissue with patchy uptake of fluorodeoxyglucose (FDG) throughout the ventricular myocardium

Genotype
MGI:5289691

cn2

• Allelic Composition: Itgb1^tm1Ross/Itgb1^tm1Ross; Tg(Hoxb7-cre)13Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:149831 )

• ~5% of mice failed to survive either birth or the first week of life due to complete bilateral renal agenesis

• all others survived into adulthood (8 weeks), indicating at least one functioning kidney

renal/urinary system

increased kidney apoptosis ( J:149831 )

• a significant increase in apoptotic (TUNEL+) cells was observed in the cortex

• a significant increase in apoptotic (TUNEL+) cells was associated with the dilated tubules in the medulla

increased kidney cell proliferation ( J:149831 )

• a significant increase in proliferative (Ki67+) cells was noted in the cortex, probably associated with proximal tubular structures, but not in the medulla

abnormal urine homeostasis ( J:149831 )

• adult mice displayed an increased urinary AVP-to-creatinine ratio (as a surrogate for plasma AVP levels)

decreased urine osmolality ( J:149831 )

• adult mice exhibited a severe decrease in urine osmolarity relative to control mice

abnormal kidney morphology ( J:149831 )

• mice exhibited a wide range of kidney abnormalities ranging from bilateral agenesis to grossly normal-sized kidneys

• mice with polyuria and renal failure showed a severely disturbed kidney architecture

abnormal kidney collecting duct morphology ( J:149831 )

• adult renal medullary collecting ducts exhibited hypoplasia, increased apoptosis, dilation (ectasia) and cyst formation

dilated kidney collecting duct ( J:149831 )

• adult renal medullary collecting ducts exhibited ectasia

abnormal kidney cortex morphology ( J:149831 )

• in adult mice, normal renal cortex areas containing clustered glomeruli were separated by larger areas with multiple cystic structures, likely to be dilated cortical collecting ducts

• a significant increase in apoptotic (TUNEL+) cells was observed in the cortex

• a significant increase in proliferative (Ki67+) cells was noted in the cortex, probably associated with proximal tubular structures, but not in the medulla

abnormal kidney medulla morphology ( J:149831 )

• in adult mice, the renal medulla exhibited tubular ectasia

• a significant increase in apoptotic (TUNEL+) cells was associated with the dilated tubules in the medulla

kidney medulla cyst ( J:149831 )

• adult renal medullary collecting ducts exhibited cyst formation

kidney medulla hypoplasia ( J:149831 )

• late-stage developing kidneys displayed a reduced inner medulla size

small kidney ( J:149831 )

• at both 1 and 2 wks of age, mutant kidneys were smaller than control kidneys

decreased kidney weight ( J:149831 )

• at both 1 and 2 weeks of age

renal hypoplasia ( J:149831 )

• at E18-P1, eleven of 25 mice showed gross renal hypoplasia, with mutant kidneys being less than 2/3 of normal size

absent kidney ( J:149831 )

• 2 of 45 mice (~5%) displayed complete bilateral renal agenesis

single kidney ( J:149831 )

• at E18-P1, one of 25 mice displayed unilateral renal agenesis

abnormal renal filtration rate ( J:149831 )

• adult kidneys exhibited a reduced capacity to clear the contrast agent DPTA from blood

abnormal renal transport ( J:149831 )

• in adult mice, renal uptake of labeled PAH was reduced ~85% relative to that of control kidneys

isosthenuria ( J:149831 )

• mutant urine remained relatively isosmotic with blood plasma

kidney failure ( J:149831 )

• in mice with polyuria and severely disturbed kidney architecture

polyuria ( J:149831 )

• at 8 weeks of age, mice had >10 times the urine output seen in control mice

• water deprivation for 12 hrs failed to reduce the urine output, unlike in control mice

• polyuria is likely due to an inability to respond to AVP within the kidney

homeostasis/metabolism

increased blood urea nitrogen level ( J:149831 )

• adult mice displayed increased plasma urea levels

abnormal urine homeostasis ( J:149831 )

• adult mice displayed an increased urinary AVP-to-creatinine ratio (as a surrogate for plasma AVP levels)

decreased urine osmolality ( J:149831 )

• adult mice exhibited a severe decrease in urine osmolarity relative to control mice

hematopoietic system

decreased hematocrit ( J:149831 )

• adult mice displayed a significantly lower blood hematocrit than control mice (42% in vs. 52%)

cellular

increased kidney apoptosis ( J:149831 )

• a significant increase in apoptotic (TUNEL+) cells was observed in the cortex

• a significant increase in apoptotic (TUNEL+) cells was associated with the dilated tubules in the medulla

increased kidney cell proliferation ( J:149831 )

• a significant increase in proliferative (Ki67+) cells was noted in the cortex, probably associated with proximal tubular structures, but not in the medulla

growth/size/body

kidney medulla cyst ( J:149831 )

• adult renal medullary collecting ducts exhibited cyst formation