Mouse choroideremia gene mutation causes photoreceptor cell degeneration and is not transmitted through the female germline

Hum Mol Genet. 1997 Jun;6(6):851-8. doi: 10.1093/hmg/6.6.851.


Choroideremia (CHM) is an X-linked progressive eye disorder which results from defects in the human Rab escort protein-1 (REP-1) gene. A gene targeting approach was used to disrupt the mouse chm/rep-1 gene. Chimeric males transmitted the mutated gene to their carrier daughters but, surprisingly, these heterozygous females had neither affected male nor carrier female offspring. The targeted rep-1 allele was detectable, however, in male as well as female blastocyst stage embryos isolated from a heterozygous mother. Thus, disruption of the rep-1 gene gives rise to lethality in male embryos; in female embryos it is only lethal if the mutation is of maternal origin. This observation can be explained by preferential inactivation of the paternal X chromosome in murine extraembryonic membranes suggesting that expression of the rep-1 gene is essential in these tissues. In both heterozygous females and chimeras the rep-1 mutation causes photoreceptor cell degeneration. Consequently, conditional rescue of the embryonic lethal phenotype of the rep-1 mutation may provide a faithful mouse model for choroideremia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases*
  • Animals
  • Blastomeres
  • Carrier Proteins / genetics*
  • Choroideremia / genetics*
  • Choroideremia / pathology
  • Disease Models, Animal
  • Female
  • Gene Targeting
  • Germ Cells
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation*
  • Photoreceptor Cells / pathology*
  • Polymerase Chain Reaction
  • rab GTP-Binding Proteins*


  • Carrier Proteins
  • Alkyl and Aryl Transferases
  • rab GTP-Binding Proteins