title: Mutation analysis provides additional proof that mottled is the mouse homologue of Menkes' disease.
abstract: Menkes' disease (MD) and occipital horn syndrome (OHS) are allelic X-linked disorders caused by mutations in the copper ion transporting ATPase, ATP7A. Genetic, phenotypic and biochemical data suggest that mottled mutants in the mouse, which range in severity and phenotype, are caused by mutations in Atp7a, the mouse homologue of ATP7A. As the only causal mutation in Atp7a has been reported in one very mild allele thought to be a model for OHS, Atp7aMo-blo (mottled blotchy), we sequenced the entire 4.5 kb coding region of three other mottled mutants, two of which are thought to be models for classical MD (AtpaMo-br, AtpaMo-13H) and one with a slightly milder phenotype (Atp7aMo-vbr). Although no causal mutation was found in Atp7aMo-13H, mutations which can be predicted to affect Atp7a function were identified in Atp7aMo-br and Atp7aMo-vbr. A 6 bp deletion of nucleotides 2478-2483, which can be predicted to affect the correct processing of the protein, was found in Atp7aMo-br and an A3189-->C nucleotide change, which results in lysine-->threonine amino acid substitution in the phosphorylation domain, was found in Atp7aMo-vbr. Thus we provide further proof that mottled mutants will provide excellent models for MD as well as OHS.
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxon, UK.
authors.forename: V
authors.initials: V
authors.lastname: Reed
authors.forename: Y
authors.initials: Y
authors.lastname: Boyd
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics; D011993:Recombinant Fusion Proteins; D017422:Sequence Analysis, DNA
chemical_list: C486201:Atp7a protein, mouse; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases