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Updated: Aug 23, 2026
Derivation of Mouse Trophoblast Stem Cells from Blastocysts
Published on: June 8, 2010
Choroideremia gene product affects trophoblast development and vascularization in mouse extra-embryonic tissues
Wei Shi1, José A J M van den Hurk, Victor Alamo-Bethencourt
1Max-Planck-Institute for Molecular Genetics, Berlin-Dahlem, Germany.
Abstract:
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.
Insights
Choroideremia (CHM) gene mutations cause embryonic lethality in mice due to extra-embryonic tissue defects. The Chm gene is crucial for placental and yolk sac development, impacting embryonic survival.
Area of Science:
- Genetics
- Developmental Biology
- Ophthalmology
Background:
- Choroideremia (CHM) is an X-linked inherited retinal disease.
- Mutations in the CHM gene cause photoreceptor degeneration.
- CHM gene disruption in mice leads to prenatal lethality.
Purpose of the Study:
- Investigate the role of the CHM gene in embryonic development.
- Identify the causes of prenatal lethality in Chm-deficient mice.
- Determine the function of Chm in extra-embryonic tissues.
Main Methods:
- Generation of Chm-deficient mouse models (Chm-/Y males and Chm-/Chm+ females).
- Analysis of embryonic development, extra-embryonic tissues (yolk sac, placenta), and vasculogenesis.
- Rescue experiments using tetraploid aggregation and interspecies breeding (Mus spretus).
Main Results:
- Chm-/Y males and Chm-/Chm+ females exhibit developmental retardation and embryonic lethality before e11.5.
- Mutant embryos show deficient diploid trophoblasts and an overabundance of giant cells.
- Severe defects in yolk sac and placental vasculogenesis are observed.
- Chm deficiency causes more severe phenotypes in males than females.
- Tetraploid aggregation and interspecies breeding rescue lethal genotypes.
Conclusions:
- The CHM gene is essential for diploid trophoblast development.
- Chm plays a critical role in placental and yolk sac vascularization.
- These functions are vital for embryonic survival, explaining the observed lethality.
