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Nonallelic noncomplementation models in mice: the first arch and lidgap-Gates mutations
1Department of Medical Genetics, University of British Columbia, Vancouver, Canada. mjharris@interchange.ubc.ca
Genome
|January 30, 1999
Summary
Two mouse mutations, Far and lgGa, showed nonallelic noncomplementation, a phenomenon termed "false allelism." This suggests that genetic background significantly influences developmental threshold defects like open eyelids.
Area of Science:
- Developmental biology
- Genetics
- Mammalian developmental defects
Background:
- Two Mendelian mutations, Far (first arch) and lgGa (lidgap-Gates), in mice are associated with a high risk of the open eyelids birth defect in homozygotes.
- These mutations are known not to be alleles, with Far mapping to Chr 2 and lgGa to Chr 13.
Purpose of the Study:
- To investigate complementation between the Far and lgGa mutations.
- To explore the phenomenon of nonallelic noncomplementation in mammalian development.
- To understand the influence of genetic background on developmental threshold defects.
Main Methods:
- Complementation testing through crosses between mice carrying Far and lgGa mutations.
- Analysis of open eyelids incidence in progeny with different genotypes.
- Evaluation of the impact of embryonic and maternal genetic background on defect risk.
Main Results:
- A cross between +/Far and lgGa/lgGa mice resulted in 32% of progeny exhibiting open eyelids, indicating noncomplementation.
- The double heterozygote (+/Far, +/lgGa) showed a 63% risk of open eyelids, significantly higher than controls.
- Genetic background strongly influenced the risk of open eyelids, with variations observed between different mouse strains and maternal backgrounds.
Conclusions:
- The Far and lgGa mutations exhibit nonallelic noncomplementation, or "false allelism," in mammals.
- This phenomenon is likely linked to developmental thresholds, where the combined effect of mutations in a specific genetic context exceeds a critical point.
- False allelism may be a common mechanism in mammalian birth defects resulting from failures to meet developmental thresholds, even with Mendelian mutations.