title: Mottled Mice and Non-Mammalian Models of Menkes Disease.
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.
authors.affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lenartowicz
authors.affiliation: Department of Cell Biology and Imaging, Institute of Zoology, Jagiellonian University Kraków, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Krzeptowski
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences Wólka Kosowska, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Lipiński
authors.affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University Kraków, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Grzmil
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences Wólka Kosowska, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Starzyński
authors.affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University Kraków, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Pierzchała
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Rigshospitalet, Copenhagen University Hospital Glostrup, Denmark.
authors.forename: Lisbeth Birk
authors.initials: LB
authors.lastname: Møller
keywords: ATP7A; Menkes disease; copper metabolism; mottled mice