PUBLICATION

Mottled Mice and Non-Mammalian Models of Menkes Disease

Authors
Lenartowicz, M., Krzeptowski, W., Lipiński, P., Grzmil, P., Starzyński, R., Pierzchała, O., Møller, L.B.
ID
ZDB-PUB-160107-10
Date
2015
Source
Frontiers in molecular neuroscience   8: 72 (Review)
Registered Authors
Keywords
ATP7A, Menkes disease, copper metabolism, mottled mice
MeSH Terms
none
PubMed
26732058 Full text @ Front. Mol. Neurosci.
Abstract
Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critical role in the maintenance of copper homeostasis in cells of the whole body. ATP7A participates in copper absorption in the small intestine and in copper transport to the central nervous system (CNS) across the blood-brain-barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Cu is essential for synaptogenesis and axonal development. In cells, ATP7A participates in the incorporation of copper into Cu-dependent enzymes during the course of its maturation in the secretory pathway. There is a high degree of homology (>80%) between the human ATP7A and murine Atp7a genes. Mice with mutations in the Atp7a gene, called mottled mutants, are well-established and excellent models of Menkes disease. Mottled mutants closely recapitulate the Menkes phenotype and are invaluable for studying Cu-metabolism. They provide useful models for exploring and testing new forms of therapy in Menkes disease. Recently, non-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals.
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