Fine mapping a major obesity locus (jObes1) using a Berlin Fat Mouse × B6N advanced intercross population
1Department for Crop and Animal Sciences, Albrecht Daniel Thaer-Institut für Agrar- und Gartenbauwissenschaften, Humboldt-Universität zu Berlin, Berlin, Germany.
International Journal of Obesity (2005)
|August 20, 2016
Summary
Researchers fine-mapped the jObes1 obesity locus in mice using an advanced intercross line. The gene Bbs7 was identified as the most likely cause of juvenile obesity, with implications for understanding fat mass regulation.
Area of Science:
- Genetics
- Obesity Research
- Animal Models
Background:
- The Berlin Fat Mouse Inbred line 860 (BFMI860) serves as a model for juvenile obesity.
- A previously identified locus, jObes1, on chromosome 3 accounts for a significant portion of total fat mass variance in BFMI860 x C57BL/6NCrl F2 populations.
Purpose of the Study:
- To perform fine-mapping of the jObes1 locus.
- To identify the specific gene(s) responsible for juvenile obesity in the BFMI860 model.
Main Methods:
- Generation of an advanced intercross line (AIL) from an F2 mapping population.
- High-density genotyping of 344 male mice using the MegaMuga chip with 22,164 SNPs.
- Phenotyping, gene expression analysis in adipose tissue, liver, and brain, and genetic complementation tests.
Main Results:
- Reduced the jObes1 confidence interval 27-fold to 0.37 Mb (36.48–36.85 Mb) with high statistical significance (LOD(BH) > 50).
- Identified Bbs7 as the most likely candidate gene, showing differential expression in multiple tissues and causing obesity in complementation tests.
- Observed that homozygous carriers of the BFMI allele had increased fat mass and, surprisingly, lower body mass until weaning.
Conclusions:
- The jObes1 locus was significantly narrowed using an AIL, pinpointing a critical region for juvenile obesity.
- Bbs7 is the prime candidate gene for jObes1, though other genes in the region cannot be fully excluded.
- Further research is required to elucidate the mechanisms underlying the observed effects on body and fat mass in juvenile mice.
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