CBA/J-Atp7a^Mo-pew/J

Stock number: 000813
Product name: pewter
Research areas: Dermatology Research, Developmental Biology Research, Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These mice carry a spontaneous mutation at the Atp7a locus characterized by a light grey coat in males and mottled coat in females due to deficiencies in a number of copper-requiring enzymes attributed to an intracellular copper transport defect.

Detailed description

The Atp7 genes encode Cu2⁺ ATPases. Atp7a is the mouse ortholog of the human ATP7A gene, which is mutated in children with Menke's syndrome. The range of defects in both Menke's syndrome and in mice having mutations of Atp7a--the mottled series of mutants--are due to deficiencies in a number of copper-requiring enzymes, in turn attributed to an intracellular copper transport defect. Thus, it is likely that the Atp7a gene product functions as a copper transport protein. (For brief review and references, see Levinson et al., 1994.)

Atp7a^Mo-pew, the mottled-pewter mutation, has the mildest effect of the known mutations at this locus. The sole phenotype noted in hemizygous males and homozygous females is their pale, silvery gray coat color. The coats of affected mice of both sexes are initially agouti; males become pewter by about 4 weeks and females at 5-6 weeks of age. Heterozygous females have normal, agouti coats throughout life. (Fox and Eicher 1978; Reynolds 2000). Both sexes are fertile (Fox and Eicher 1978).

At the molecular level, the Atp7a^Mo-pew mutation consists of a single point mutation at nucleotide 3074, in exon 15. The G-->A transition causes the substitution of a threonine for an alanine. The affected amino acid occurs in a seven amino acid sequence that is highly conserved among the twenty-one known or presumed copper-transporting ATPases. This sequence comprises the transduction domain in the sixth transmembrane segment of the protein and is believed to be responsible for its copper binding and transport functions (Levinson et al., 1997.)

Development

Atp7a^Mo-pew occurred spontaneously in 1976 on the CBA/J inbred strain at The Jackson Laboratory.

Allele

Symbol: Atp7a^Mo-pew
Name: pewter
MGI accession ID: MGI:1856104
Generation method: Spontaneous
Marker symbol: Atp7a
Marker name: ATPase, Cu++ transporting, alpha polypeptide
Chromosome: X
Strain of origin: CBA/J
Molecular note: This allele comprises a G-to-A substitution at coding nucleotide 2995 in exon 15 creating a missense mutation that alters codon 999 from an alanine to a threonine in a conserved region of the transduction domain of the encoded protein.