caa a22 4500 397573626 CHVBK 20180308164848.0 cr unu---uuuuu 161202e199610 xx s 000 0 eng 10.1093/hmg/5.10.1619 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.10.1619 The Toxic Milk Mouse is a Murine Model of Wilson Disease [Elektronische Daten] [Michael B. Theophilos, Diane W. Cox, Julian F. B. Mercer] Wilson disease (WD) is an autosomal recessive defect of copper transport characterized by massive accumulation of copper in the liver, which can lead to liver failure. Mutations in a copper transporting ATPase (WND or ATP7B) have been shown to cause the disease.The toxic milk mouse mutant (tx) accumulates copper in the liver in a manner similar to that observed in patients with WD. However, some physiological differences between tx mice and human WD patients have cast doubts on whether this mutant mouse is a valid model for WD. In this paper we report the isolation of cDNA clones encoding the murine homologue of WND. The predicted amino acid sequence is 1462 amino acids and contains the same functional domains identified in human and rat WND. As in the rat, the fourth metal binding domain is apparently non-functional. Similar levels of a 7.5 kb WND mRNA were detected in liver and kidney from normal and txmice, indicating that transcription of this gene was unaffected in the mutant mice. The coding sequence of WND cDNA from the tx mouse liver identified a single nucleotide difference between the normal DL mouse and the tx which is predicted to change methionine1356 in the eighth transmembrane domain to valine. This methionine is conserved in all copper ATPases including those from bacteria and yeast. The conclusion that this is the causative mutation is supported by the recent mapping of tx and WND to the same region of mouse chromosome 8. Thus the tx mouse is presented as a valid model for studies of the role of WND in copper transport and for investigation of different treatment strategies for WD. © 1996 Oxford University Press Theophilos Michael B. Scobie and Clare Mackinnon Trace Element Laboratory, Murdoch Institute, Royal Children's Hospital, Flemington Road, Parkville 3052, Australia aut Cox Diane W. Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada aut Mercer Julian F. B. Scobie and Clare Mackinnon Trace Element Laboratory, Murdoch Institute, Royal Children's Hospital, Flemington Road, Parkville 3052, Australia aut Human Molecular Genetics Oxford University Press 5/10(1996-10), 1619-1624 0964-6906 5:10<1619 1996 5 hmg https://doi.org/10.1093/hmg/5.10.1619 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.10.1619 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Theophilos Michael B. Scobie and Clare Mackinnon Trace Element Laboratory, Murdoch Institute, Royal Children's Hospital, Flemington Road, Parkville 3052, Australia aut NATIONALLICENCE 700 1- Cox Diane W. Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada aut NATIONALLICENCE 700 1- Mercer Julian F. B. Scobie and Clare Mackinnon Trace Element Laboratory, Murdoch Institute, Royal Children's Hospital, Flemington Road, Parkville 3052, Australia aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/10(1996-10), 1619-1624 0964-6906 5:10<1619 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford