Nature Genetics
6, 374 - 378 (1994)
doi:10.1038/ng0494-374
Mutations in the murine homologue of the Menkes gene in dappled and blotchy miceJulian F.B. Mercer1, Andrew Grimes1, Loreta Ambrosini1, Paul Lockhart1, Jennifer A. Paynter1, Herman Dierick2, 3
& Thomas W. Glover2, 3
1Scobie and Claire Mackinnon Trace Element Group, Murdoch Institute, Parkville, Victoria 3052, Australia
2Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
3Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA Correspondence should be addressed to J.F.B.M. The murine homologue of the Menkes disease gene (MNK) was isolated from cDNA libraries, using human cDNA clones as probes, and by PCR. The predicted amino acid sequence shows a high level of identity (89.9%) with the human protein, and the predicted functional domains in the human protein are present. Using probes to the mouse Mnk gene, we found that the mottled dappled mutation was caused by alteration in the Mnk locus and lack of expression of Mnk RNA. Tissues of the blotchy mouse contained two larger sizes of MNK mRNA demonstrating a likely defect in RNA splicing. Thus, the mottled locus is homologous to the human MNK locus and dappled and blotchy are allelic mutations in this gene.
REFERENCES
- Lyon, M.F. & Searle, A.G. Mo locus, ChrX In Genetic Variants and Strains of the Laboratory Mouse (eds Lyon, M.F. & Searle, A.G.) 241−244 (Oxford University Press, Oxford, 1990). | ChemPort |
- Camakaris, J., Mann, J.R. & Danks, D.M. Copper metabolism in mottled mouse mutants: copper concentrations in tissues during development. Biochem. J. 180, 597−604 (1979). | PubMed | ISI | ChemPort |
- Danks, D.M. Disorders of copper transport In The Metabolic Basis of Inherited Disease (eds Scriver, C.R. et al.) 1411−1431 (McGraw-Hill, New York, 1989).
- Nielson, J.T. & Chapman, V.M. Electrophoretlc variants for X-chromosome-linked phosphoglycerate kinase (PGK-1) in the mouse. Genetics 87, 319−325 (1977).
- Phillips, M., Camakaris, J. & Danks, D.M. Comparisons of copper deficiency states In the murine mutants blotchy and brindled. Biochem. J. 238, 177−183 (1986). | PubMed | ISI | ChemPort |
- Phillips, R.J.S.'Dappled' a new allele at the mottled locus in the house mouse. Genet. Res. 2, 209−295 (1961).
- Chelly, J. et al. Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. Nature Genet. 3, 14−19 (1993). | PubMed | ISI | ChemPort |
- Mercer, J.F.B. et al. Isolation of a partial candidate gene for Menkes disease by positional cloning. Nature Genet. 3, 20−25 (1993). | PubMed | ISI | ChemPort |
- Vulpe, C., Levinson, B., Whitney, S., Packman, S. & Gitschier, J. Isolation of a candidate genefor Menkes disease and evidence that it encodes a copper-transporting ATPase. Nature Genet. 3, 7−13 (1993). | PubMed | ISI | ChemPort |
- Levinson, B. et al. The mottled gene is the mouse homologue of the Menkes gene. Nature Genet. 6, 369−373 (1994). | Article | PubMed | ISI | ChemPort |
- Vulpe, C., Levinson, B., Whitney, S., Packman, S. & Gitschier, J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. (Correction) Nature Genet. 3, 273 (1993). | ISI | ChemPort |
- Gubbay, J. et al. A gene mapping to the sex-determlng region of the mouse Y-chromosome is a member of a novel family of embryonically expressed genes. Nature 346, 245−250 (1990). | Article | PubMed | ISI | ChemPort |
- Silver, S., Nucifora, G., Chu, L. & Misra, T.K. Bacterial resistance ATPases: primary pumps for exporting toxic cations and anions Trends in. Biochem. Sci. 14, 76−80 (1989). | Article | ChemPort |
- Goodhead, D.T., Thacker, J. & Cox, R. Effects of radiations of different qualities on cells: molecular mechanisms of damage and repair. Int. J. radiat. Biol. 63, 543−556 (1993). | PubMed | ISI | ChemPort |
- Heydorn, K. et al. Extrahepatic storage of copper: a male fetus suspected of Menkes disease. Humangenetik 29, 171−175 (1975). | PubMed | ISI |
- Paynter, J.A., Camakaris, J. & Mercer, J.F.B. Analysis of hepatic copper, zinc, metallothionein and metallothionein-la in the developing sheep. Eur. J. Biochem. 190, 149−154 (1990). | PubMed | ISI | ChemPort |
|
