title: Phenotypic and genetic characterization of the Atp7a(Mo-Tohm) mottled mouse: a new murine model of Menkes disease.
abstract: Mottled Tohoku (Atp7a(Mo-Tohm) or Mo(Tohm)) is an X-linked mutation with mottled pigmentation in heterozygous (Mo(Tohm)/+) females and is embryonic lethal at E11 in hemizygous (Mo(Tohm)/Y) males. Copper levels were low in the brain and high in the intestine of Mo(Tohm) mice. Two congenic strains with ICR or C57BL/6 (B6) background were produced for genetic and phenotypic analyses and revealed that Mo(Tohm)/+ females with ICR background survived until adulthood, while most with B6 background died within 2 days after birth. The Mo(Tohm)/Y males with both backgrounds died at around E11. Massive hemorrhage was shown in the yolk sac cavity with irregular attachment between the mesoderm and the endothelial cells of blood vessels in the embryos at E10.5, suggesting that this irregular attachment causes embryonic lethality. The Mo(Tohm) mutant had a 1440-bp deletion between intron 22 and exon 23 of the Atp7a gene. Mo(Tohm)/Y males with the wild-type Atp7a cDNA transgene were rescued from embryonic lethality, confirming that the Mo(Tohm) mutant is caused by the defect in the Atp7a gene. This mutant mouse is the most severe model of human Menkes disease in mottled mice established to date and one of the useful models for understanding the gene function of Menkes disease.
authors.affiliation: Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-7585, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Mototani
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Xiang
authors.initials: X
authors.lastname: Yuan Pei
authors.forename: Satomi
authors.initials: S
authors.lastname: Kameo
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasai
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D005804:Genes, Lethal; D020287:In Situ Nick-End Labeling; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D019076:Transgenes
chemical_list: C486201:Atp7a protein, mouse; D027682:Cation Transport Proteins; D017931:DNA Primers; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases