Phenotypic and genetic characterization of the Atp7aMo-Tohm mottled mouse: A new murine model of Menkes disease

Yasumasa Mototani, Ichiro Miyoshi, Tadashi Okamura, Takuya Moriya, Yan Meng, Xiang Yuan Pei, Satomi Kameo, Noriyuki Kasai

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Mottled Tohoku (Atp7aMo-Tohm or MoTohm) 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 MoTohm mice. Two congenic strains with ICR or C57BL/6 (B6) background were produced for genetic and phenotypic analyses and revealed that MoTohm/+ 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 MoTohm mutant had a 1440-bp deletion between intron 22 and exon 23 of the Atp7a gene. MoTohm/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.

Original languageEnglish
Pages (from-to)191-199
Number of pages9
Issue number2
Publication statusPublished - 2006 Feb
Externally publishedYes


  • Atp7a
  • Copper deficiency
  • Embryonic lethality
  • Menkes disease
  • Mottled mouse
  • Transgene
  • Yolk sac

ASJC Scopus subject areas

  • Genetics


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