Inbred mouse strains and genetic stability: a review

Area of Science:

• * Laboratory animal science
• * Genetics and genomics
• * Biomedical research

Background:

• * Inbred mice have been indispensable animal models for scientific research for over a century.
• * Despite their widespread use, the genetic properties of inbred strains, particularly their homogeneity and stability, have been underestimated.
• * Recent research highlights genetic fragility and instability in inbred mouse populations.

Purpose of the Study:

• * To review current understanding of genetic homogeneity and stability in laboratory inbred mouse strains.
• * To discuss recent findings on genetic variability within inbred mouse populations.
• * To re-evaluate the suitability of inbred mice as research models in light of new genetic insights.

Main Methods:

• * Literature review of recent studies on inbred mouse genetics.
• * Analysis of genetic variability, including single-gene mutations and polygenic variation.
• * Consideration of factors influencing genetic heterogeneity, such as heterozygote selection and genetic drift.

Main Results:

• * Inbred mice are not completely isogenic; they harbor new genetic polymorphisms from mutations and polygenic variability.
• * New mutations are continuously introduced, and small mutations can account for significant phenotypic variance (e.g., 4.5% in C57BL/6J).
• * Genetic heterogeneity can persist through selection and drift, and while contamination is minimal, it's a factor.

Conclusions:

• * Inbred mice exhibit unavoidable moderate-to-low genetic variability, challenging the assumption of complete isogenicity.
• * Despite this heterogeneity, inbred mice remain remarkably homogeneous and advantageous compared to highly variable outbred populations.
• * Inbred mice continue to be essential and highly useful models for current and future scientific research.