After GWAS: mice to the rescue?

Area of Science:

• Immunology
• Genetics
• Translational Medicine

Background:

• The genetic underpinnings of human autoimmune diseases are not fully understood, despite advances from genome-wide association studies (GWAS).
• Mouse models offer valuable tools to bridge knowledge gaps identified by human genetic studies.

Purpose of the Study:

• This review explores how mouse genetic studies can complement human genetic data to elucidate autoimmune disease mechanisms.
• It highlights the utility of forward and reverse genetic approaches in identifying and validating disease-associated genes.

Main Methods:

• Discusses forward genetic strategies like mutagenesis screens and quantitative trait locus (QTL) mapping to identify candidate genes.
• Explains reverse genetic approaches using genetically engineered mice to functionalize disease-associated genes and variants.
• Addresses the role and characteristics of inbred mouse strains in genetic research.

Main Results:

• Mouse studies, particularly using inbred strains, facilitate the identification and functional analysis of genes implicated in autoimmune diseases.
• Acknowledges complexities in translating mouse findings to humans, including species-specific differences, genetic background effects, and microbial influences.

Conclusions:

• Mice are indispensable tools for autoimmune disease research in the post-GWAS era, aiding in the discovery of genetic factors.
• Careful consideration of genetic background and environmental factors is crucial for robust and translatable findings.