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Mapping liver fat female-dependent quantitative trait loci in collaborative cross mice
Hanifa J Abu-Toamih Atamni1, Maya Botzman2, Richard Mott3
1Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel.
Summary
Genetic factors influence non-alcoholic fatty liver disease (NAFLD) development. This study identified specific quantitative trait loci (QTLs) for hepatic fat accumulation in female mice using the Collaborative Cross model.
Area of Science:
- Genetics
- Hepatology
- Metabolic Diseases
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition.
- Host genetics significantly impact NAFLD development and progression.
- Understanding genetic underpinnings is crucial for therapeutic strategies.
Purpose of the Study:
- To utilize the Collaborative Cross (CC) mouse model to identify genetic loci controlling hepatic fat accumulation.
- To investigate sex-specific genetic contributions to fatty liver in mice.
Main Methods:
- Employed the Collaborative Cross (CC) mouse resource with 168 female and 338 male mice.
- Assessed hepatic fat content using dual-energy X-ray absorptiometry (DEXA) scans.
- Performed quantitative trait loci (QTL) mapping using high-density genotype data.
Main Results:
- Identified three significant QTLs for hepatic fat accumulation, named Flal1-Flal3, on chromosomes 17, 18, and 4, exclusively in female mice.
- No significant QTLs associated with liver fat accumulation were detected in male mice.
- Candidate genes involved in hepatic fat metabolism were suggested by genome database searches.
Conclusions:
- Hepatic fat accumulation is a complex trait influenced by multiple genetic factors in female mice.
- Genetic control of fatty liver accumulation appears to be sex-specific, with distinct mechanisms in males and females.
- The CC mouse model is a powerful tool for dissecting the genetic architecture of complex liver diseases like NAFLD.
