Human Molecular Genetics, Vol 6, 1043-1049, Copyright © 1997 by Oxford University Press
YM Kuo, J Gitschier and S Packman
Menkes disease and Wilson disease are human disorders of copper transport
caused by mutations in distinct genes encoding similar copper- transporting
P-type ATPases. These genes are expressed in different adult tissues in
patterns reflecting disease manifestations. The mouse homologues for the
Menkes (MNK) and Wilson (WND) disease genes are the mottled (Atp7a) and
toxic milk (Atp7b) genes, respectively. Using RNA in situ hybridization we
describe the distribution of mottled and toxic milk transcripts during
mouse embryonic development. The mottled gene is expressed in all tissues
throughout embryogenesis and is particularly strong in the choroid plexuses
of the brain. Mottled expression in the liver is in contrast to the prior
observation of absent or very low expression in the adult liver. Expression
of the toxic milk gene is significantly more delimited, with early
expression in the central nervous system, heart and liver. Later in
gestation, toxic milk transcript is clearly seen in the liver, intestine,
thymus and respiratory epithelium including nasopharynx, trachea and
bronchi. In lung, toxic milk expression is restricted to bronchi, while
mottled expression is diffuse. Hepatic expression of both toxic milk and
mottled is in the parenchyma, as opposed to blood cells. These results
suggest that the mottled gene product functions primarily in the
homeostatic maintenance of cell copper levels, while the toxic milk gene
product may be specifically involved in the biosynthesis of distinct
cuproproteins in different tissues.
ARTICLES
Developmental expression of the mouse mottled and toxic milk genes suggests distinct functions for the Menkes and Wilson disease copper transporters
Department of Medicine, University of California, San Francisco 94143, USA.
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