Phenotypes associated with this allele

• Allele Symbol: Atox1^{Gt(IRESBetageo)3Pgr}
• Allele Name: gene trap 3, Peter Gruss
• Allele ID: MGI:2158341
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atox1^Gt(IRESBetageo)3Pgr/Atox1^Gt(IRESBetageo)3Pgr	B6.129(Cg)-Atox1^Gt(IRESBetageo)3Pgr/Mmucd	MGI:2677161

Genotype
MGI:2677161

hm1

• Allelic Composition: Atox1^{Gt(IRESBetageo)3Pgr}/Atox1^{Gt(IRESBetageo)3Pgr}
• Genetic Background: B6.129(Cg)-Atox1^{Gt(IRESBetageo)3Pgr}/Mmucd

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:74249 )

• 46% of mutant pups born from heterozygous male homozygous female crosses die within 24 hrs after birth

• 20% of mutant pups born from homozygous male heterozygous female crosses die within 24 hrs after birth

postnatal lethality, incomplete penetrance ( J:74249 )

• ~45% of homozygotes derived from heterozygous matings die prior to weaning age

• specifically, 33% die by P3 and an additional 12% die from prolonged seizure activity before weaning

growth/size/body

decreased body size ( J:74249 )

• surviving homozygotes derived from heterozygous matings are smaller than wild-type littermates

postnatal growth retardation ( J:74249 )

• by P3, most homozygotes derived from heterozygous matings display a symmetrical growth retardation relative to wild-type littermates; homozygotes that survive beyond weaning remain growth-retarded

• maternal deficiency increases the severity of growth retardation

behavior/neurological

decreased locomotor activity ( J:74249 )

• at P3, homozygotes derived from heterozygous matings display reduced activity

• however, sucking behavior, serum glucose levels, hematocrit and electrolyte values are within normal range

seizures ( J:74249 )

• 12% of homozygotes derived from heterozygous matings die from prolonged seizure activity before weaning

pigmentation

hypopigmentation ( J:74249 )

• surviving homozygotes derived from heterozygous matings show hypopigmentation of the tail and coat color

• maternal deficiency increases the severity of hypopigmentation because of little or no tyrosinase activity

cardiovascular system

internal hemorrhage ( J:74249 )

• some newborn homozygotes derived from heterozygous matings display peripartum abdominal hemorrhage

pulmonary alveolar hemorrhage ( J:74249 )

• some newborn homozygotes derived from heterozygous matings exhibit pulmonary alveolar hemorrhage

respiratory system

pulmonary alveolar hemorrhage ( J:74249 )

• some newborn homozygotes derived from heterozygous matings exhibit pulmonary alveolar hemorrhage

homeostasis/metabolism

decreased body temperature ( J:74249 )

• surviving homozygotes derived from heterozygous matings are hypothermic

abnormal copper homeostasis ( J:74249 )

• homozygotes display impaired perinatal copper homeostasis, as shown by diminished placental copper transfer to homozygous mutant embryos, where copper retention within the placenta due to defective cellular copper efflux results in reduced copper availability for the fetal circulation

• in vitro, mouse embryonic fibroblasts (MEFs) isolated from E12.5 homozygous mutant embryos accumulate higher levels of intracellular copper than wild-type MEFs due to a severe defect in cellular copper efflux

• at P2, the activity of essential cupro-enzymes including brain cytochrome oxidase and skin tyrosinase is significantly reduced

• maternal deficiency significantly increases the severity of copper deficiency in homozygous mutant pups

decreased brain copper level ( J:74249 )

• at P2, mutant pups derived from heterozygous matings show a 50% reduction of copper content in the brain

decreased liver copper level ( J:74249 )

• at P2, mutant pups derived from heterozygous matings contain 50% less copper in the liver relative to wild-type pups

abnormal enzyme/coenzyme activity ( J:74249 )

• at P2, mutant pups derived from heterozygous matings show a 36.5% reduction in brain cytochrome oxidase activity and a ~75% reduction in skin tyrosinase activity, indicating that the activity of essential cupro-enzymes is significantly diminished

• maternal deficiency results in a near complete absence of tyrosinase activity in skin tissue extracts

• in contrast, the activity of succinate dehydrogenase remains normal

liver/biliary system

decreased liver copper level ( J:74249 )

• at P2, mutant pups derived from heterozygous matings contain 50% less copper in the liver relative to wild-type pups

vision/eye

microphthalmia ( J:74249 )

• ~9% (6 of 68) of mutant pups born to homozygous, but not to heterozygous, mothers displayed microphthalmia; only one mouse survived past P3

nervous system

seizures ( J:74249 )

• 12% of homozygotes derived from heterozygous matings die from prolonged seizure activity before weaning

abnormal nervous system morphology ( J:74249 )

• occasional mutant pups born to homozygous, but not to heterozygous, mutant mothers exhibit CNS abnormalities and other developmental anomalies not observed in control littermates

decreased brain copper level ( J:74249 )

• at P2, mutant pups derived from heterozygous matings show a 50% reduction of copper content in the brain

integument

loose skin ( J:74249 )

• newborn homozygotes derived from heterozygous matings display skin laxity

• maternal deficiency increases the severity of skin laxity

cellular

maternal effect ( J:74249 )

• mutant pups born to homozygous mutant mothers display a more severe growth retardation, skin laxity, and hypopigmentation phenotype than that observed in mutant pups derived from heterozygous mothers

• mutant pups born to homozygous mutant mothers display a near complete absence of tyrosinase enzyme activity in skin tissue extracts

• mutant pups born to homozygous mutant mothers exhibit increased mortality within the first day of life: 46% die within 24 hrs after birth from heterozygous male homozygous female crosses, whereas 20% die within that time period from homozygous male heterozygous female crosses

• mutant pups born to homozygous mutant mothers display an overall reduction of 60% in copper availability for placental transport

• ~9% (6 of 68) of mutant pups born to homozygous, but not to heterozygous, mothers displayed microphthalmia; only one mouse survived past P3

• in addition, occasional mutant pups born to homozygous mutant mothers exhibit CNS abnormalities and other developmental anomalies not observed in control littermates