| First Author | Kelly EJ | Year | 1996 |
| Journal | Nat Genet | Volume | 13 |
| Issue | 2 | Pages | 219-22 |
| PubMed ID | 8640230 | Mgi Jnum | J:33276 |
| Mgi Id | MGI:80756 | Doi | 10.1038/ng0696-219 |
| Citation | Kelly EJ, et al. (1996) A murine model of Menkes disease reveals a physiological function of metallothionein. Nat Genet 13(2):219-22 |
| abstractText | Human Menkes disease and the murine Mottled phenotype are X-linked diseases that result from copper deficiency due to mutations in a copper-effluxing ATPase, designated ATP7A. Male mice with the Mottled-Brindled allele (Mo-brJ) accumulate copper in the intestine, fail to export copper to peripheral organs and die a few weeks after birth. Much of the intestinal copper is bound by metallothionein (MT). To determine the function of MT in the presence of Atp7a deficiency, we crossed Mo-brJ females with males that bear a targeted disruption of the Mt1 and Mt2 genes (Mt-/-). On an Mt -/- background, most Mo-brJ males as well as heterozygous Mo-brJ females die before embryonic day 11. The lethality in Mo-brJ females can be explained by preferential inactivation of the paternal X chromosome in extraembryonic tissues and resultant copper toxicity in the absence of MT. In support of this hypothesis, cell lines derived from Mt -/-, Mo-brJ embryos are very sensitive to copper toxicity. |
