Related Experiment Videos
Effects of the lethal yellow (Ay) mutation in mouse aggregation chimeras
G S Barsh1, M Lovett, C J Epstein
1Department of Pediatrics, University of California, San Francisco 94143.
Development (Cambridge, England)
|July 1, 1990
Summary
The Ay allele causes embryonic death in mice, but heterozygotes show adult-onset obesity. This study used mouse chimeras to show that Ay heterozygosity affects weight gain in a cell-non-autonomous manner.
Area of Science:
- Genetics
- Developmental Biology
- Obesity Research
Background:
- The Ay allele in mice is a recessive lethal mutation causing embryonic death.
- Heterozygous Ay/a mice exhibit dominant traits like increased weight gain, tumor susceptibility, and yellow coat color.
Purpose of the Study:
- To investigate the cellular mechanisms of the Ay allele's effects on embryonic viability and adult-onset obesity.
- To determine if Ay heterozygosity's impact on weight gain is cell-autonomous or cell-non-autonomous.
Main Methods:
- Generation of aggregation chimeras by combining embryos with different agouti locus genotypes (Ay/a and A/A).
- Genotypic identification of chimeras using a molecular probe at the Emv-15 locus.
- Analysis of embryonic viability and adult-onset obesity in liveborn and embryonic chimeras.
Main Results:
- Absence of Ay/Ay cells in chimeras indicates they cannot be rescued, even in a chimeric environment.
- A relative deficiency of Ay/a cells suggests potential impacts on cell viability or proliferation under certain conditions.
- Liveborn Ay/a in equilibrium A/A chimeras developed obesity, while a/a in equilibrium A/A chimeras did not.
- No correlation between genotypic proportions and weight gain rate was observed.
Conclusions:
- Ay/Ay cells are not viable even in a supportive chimeric environment.
- Ay heterozygosity's effect on adult-onset obesity is cell-non-autonomous, meaning it is influenced by signals from surrounding cells.
- The Ay allele presents complex effects on embryonic development and adult physiology, with implications for understanding genetic contributions to obesity.