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Chromosome substitution strains: gene discovery, functional analysis, and systems studies
Joseph H Nadeau1, Jiri Forejt, Toyoyuki Takada
1Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA. jnadeau.pnri@gmail.com
Summary
Chromosome substitution strains (CSSs) in mice enable gene discovery for complex traits and diseases. These engineered strains reveal genetic diversity, epistasis, and epigenetic changes, aiding in identifying quantitative trait loci (QTLs).
Area of Science:
- Genetics
- Genomics
- Animal Models
Background:
- Laboratory mice are crucial for biomedical research due to diverse genetic resources.
- Chromosome substitution strains (CSSs) are vital for studying complex genetic traits and modeling human diseases.
Purpose of the Study:
- To highlight the utility of CSSs in laboratory mice for gene discovery and functional characterization.
- To demonstrate the application of CSS panels in dissecting phenotypic diversity and disease models.
Main Methods:
- CSSs are created by replacing a host strain's chromosome with one from a donor strain.
- A complete CSS panel includes 22 engineered strains (19 autosomes, X, Y, mitochondria).
- Genome surveys involve comparing CSS phenotypes to the host strain.
Main Results:
- CSS panels have dissected diverse phenotypes and characterized numerous disease models.
- Studies revealed significant phenotypic diversity, epistasis, and heritable epigenetic changes.
- CSSs facilitate the identification and functional characterization of genetic variants underlying quantitative trait loci (QTLs).
Conclusions:
- CSSs are indispensable resources in laboratory mice for genetic research.
- These strains are powerful tools for understanding complex genetic traits and diseases.
- CSSs and derived congenic strains accelerate the identification of QTLs and their functional roles.
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