Phenotypes Associated with This Genotype

Genotype
MGI:3043693

• Allelic Composition: Atp7b^tm1Tcg/Atp7b^tm1Tcg
• Genetic Background: involves: 129S1/Sv

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:57632 )

• in a few litters, the second generation of pups born to homozygous mutant dams died by the age of 3 weeks; however, in the remaining litters, most of the pups survived and appeared normal by the age of 5-6 weeks

behavior/neurological

tremors ( J:57632 )

• the second generation of pups born to homozygous mutant dams displayed tremors

abnormal locomotor behavior ( J:57632 )

• the second generation of pups born to homozygous mutant dams displayed abnormal locomotive behavior

ataxia ( J:57632 )

• the second generation of pups born to homozygous mutant dams displayed ataxia

endocrine/exocrine glands

abnormal mammary gland physiology ( J:57632 )

♀ • the apparently copper-laden mammary glands in homozygous mutant females produced copper-deficient milk

♀ • a similar "infant syndrome" has been reported for mutant pups born to homozygous mutant dams with "toxic milk"

growth/size/body

postnatal growth retardation ( J:57632 )

• the progeny of homozygous mutant females displayed growth retardation

homeostasis/metabolism

abnormal copper level ( J:57632 )

• homozygotes displayed gradual copper accumulation in the liver, kidney, brain, placenta and lactating mammary glands

• no significant copper deposition was detected in the iris

• despite copper accumulation in these tissues, young to middle-aged adult mutants were viable, fertile, and overtly normal

• copper levels in the mutant placenta were elevated about 4-fold relative to wild-type

abnormal liver copper level ( J:57632 )

• by 5 months of age, accumulation of hepatic copper increased to a level 60-fold greater than wild-type

• newborn homozygotes displayed about a 30-fold reduction in hepatic copper relative to wild-type

liver/biliary system

liver/biliary system phenotype ( J:57632 )

N • no jaundice, ascitis or other signs of liver decompensation were observed until 10 months of age

abnormal liver morphology ( J:57632 )

• accumulation of hepatic copper in young homozygotes led to the formation of regenerative (cirrhotic) nodes and subsequent fibrosis in middle- to old-aged mice (>7 months)

abnormal liver copper level ( J:57632 )

• by 5 months of age, accumulation of hepatic copper increased to a level 60-fold greater than wild-type

• newborn homozygotes displayed about a 30-fold reduction in hepatic copper relative to wild-type

liver cirrhosis ( J:57632 )

• accumulation of hepatic copper in young homozygotes led to the formation of regenerative (cirrhotic) nodes and subsequent fibrosis in middle- to old-aged mice (>7 months)

integument

abnormal mammary gland physiology ( J:57632 )

♀ • the apparently copper-laden mammary glands in homozygous mutant females produced copper-deficient milk

♀ • a similar "infant syndrome" has been reported for mutant pups born to homozygous mutant dams with "toxic milk"

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Wilson disease		DOID:893	OMIM:277900	J:57632