Choroideremia gene product affects trophoblast development and vascularization in mouse extra-embryonic tissues

Dev Biol. 2004 Aug 1;272(1):53-65. doi: 10.1016/j.ydbio.2004.04.016.


Choroideremia (CHM) is a hereditary eye disease caused by mutations in the X-linked CHM gene. Disruption of the Chm gene in mice resulted in prenatal death of Chm-/Y males and Chm-/Chm+ females that had inherited the mutation from their mothers. Male chimeras and Chm+/Chm- females with paternal transmission of the mutation were viable and had photoreceptor degeneration reminiscent of human choroideremia. Here, we show that Chm-/Y males and Chm-/Chm+ females were retarded at e7.5 and died before e11.5 due to multiple defects of the extra-embryonic tissues. Mutant embryos exhibited deficiency of diploid trophoblasts associated with overabundance of giant cells. In yolk sac and placenta, severe defects in vasculogenesis were obvious. Chm-/Y males exhibited more pronounced phenotypes than Chm-/Chm+ females. The lethal genotypes could be rescued by tetraploid aggregation. Chm-/Chm+ females, but not Chm-/Y males, could also be rescued when their Chm+/Chm- mothers were mated with Mus spretus males. Backcross analysis suggested that the viability of interspecies hybrid Chm-/Chm+ females may be due to expression from the Chm allele on the M. spretus X-chromosome rather than a modifier effect. Our results demonstrate that Chm is essential for diploid trophoblast development and plays a role in the vascularization in placenta and yolk sac.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / genetics*
  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Blood Vessels / embryology*
  • Blood Vessels / physiology
  • Breeding
  • Embryo, Mammalian / blood supply*
  • Eye / pathology
  • Female
  • Fetal Death / genetics
  • Gene Expression Regulation, Developmental*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Placenta / pathology
  • Polyploidy
  • Pregnancy
  • Trophoblasts / physiology*
  • X Chromosome
  • Y Chromosome
  • Yolk Sac / blood supply
  • Yolk Sac / pathology


  • Alkyl and Aryl Transferases