Human Molecular Genetics, Vol 6, 417-423, Copyright © 1997 by Oxford University Press
V Reed and Y Boyd
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.
ARTICLES
Mutation analysis provides additional proof that mottled is the mouse homologue of Menkes' disease
MRC Mammalian Genetics Unit, Harwell, Oxon, UK.
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