title: Alternative splicing in the Atp7a gene in the Cu deficient mosaic mutation in mice.
abstract: The X-linked mosaic mutation in mice belongs to the mottled group of mutations. This group represents animal models of human copper deficiency disease, such as Menkes disease. It has been demonstrated that the disruption of copper metabolism is caused by a mutation in the Atp7a gene and leads to a lethal phenotype. Many similarities between mosaic and other mottled mutants give a strong indication that this mutation could occur in the cDNA of the Atp7a gene. In this paper, the cDNA of this gene was sequenced from 9 unrelated mutants and 7 unrelated control mice. It was found that a CAG insertion at the end of the 4th exon exists in the mutants but not in control cDNA. The same CAG insertion was previously described as a polymorphism in alternative splicing between BALB/c and C57BL/6 mice, therefore it is suggested that this changed sequence is a polymorphism strongly related to the phenotype rather than it is the cause of mutation. However, such a strong linkage between this polymorphism and the mosaic phenotype (lasting for 96 outbred generations), suggests that the mutation is in the Atp7a gene.
authors.affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University, R. Ingardena 6, 30-060 Krakow, Poland. lena@zuk.iz.uj.edu.pl
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lenartowicz
authors.forename: Paweł
authors.initials: P
authors.lastname: Grzmil
authors.forename: Marek
authors.initials: M
authors.lastname: Rusin
authors.forename: Józefa
authors.initials: J
authors.lastname: Styrna
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D017398:Alternative Splicing; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C486201:Atp7a protein, mouse; D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases