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Host Genetic Background Effect on Body Weight Changes Influenced by Heterozygous Smad4 Knockout Using Collaborative
Nayrouz Qahaz1, Iqbal M Lone1, Aya Khadija1
1Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel.
International Journal of Molecular Sciences
|November 25, 2023
Summary
Researchers used mouse models to study genetic predispositions to obesity. They found that the Smad4 gene mutation generally caused overweight in mice, with varying effects based on genetic background. Machine learning accurately predicted mouse genotypes.
Area of Science:
- Genetics
- Obesity Research
- Animal Models
Background:
- Obesity is a global health crisis with complex genetic and environmental causes.
- Mouse models offer a controlled environment to study genetic factors influencing body weight gain.
- The Collaborative Cross (CC) mouse resource provides diverse genetic backgrounds for trait analysis.
Purpose of the Study:
- To investigate the impact of heterozygous Smad4 knockout on body weight gain in different Collaborative Cross (CC) mouse lines.
- To estimate the heritability of body weight and related traits.
- To compare machine learning algorithms for predicting body weight changes and mouse genotypes.
Main Methods:
- Crossed Smad4+/- male mice with female mice from 10 CC lines to create F1 hybrids.
- Monitored body weight weekly until 16 weeks, then monthly until 48 weeks.
- Estimated heritability (H2) and applied machine learning (logistic regression) for genotype prediction.
Main Results:
- Significant differences in body weight gain were observed between wild-type and Smad4 mutant F1 mice across CC lines.
- Genetic background modulated the effect of Smad4 knockout on body weight, with most lines showing increased weight.
- Heritability of body weight was higher in females than males and higher in wild-type than mutant genotypes.
- Logistic regression demonstrated the highest accuracy for predicting mouse genotypes.
Conclusions:
- The Smad4 gene plays a role in regulating body weight, with its effect influenced by the genetic background of the mouse.
- Heritability estimates provide insights into the genetic contribution to body weight regulation.
- Machine learning, particularly logistic regression, is a valuable tool for predicting genotypes and understanding complex traits in mouse models.
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