Chromosome 1 substitution strains, a new resource for pre-clinical MASLD mouse model development

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease and is the leading cause of liver-related morbidity and mortality. However, neither the diet induction model nor the monogenic model based on the laboratory mice could fully imitate human MASH due to the genetic background of existing inbred mice have limitations, such as the lack of genetic diversity and reduced disease susceptibility. Comparing with the laboratory mice, wild mice harbor more genetic polymorphisms to adapt to the natural environment, therefore, introducing the genetic material from wild mice into inbred mice would provide new experiments resources for the complex trait researches. Therefore, GemPharmatech has launched “Wild Mouse” project to develop a complete set of consomics covering all 19 autosomes of mouse, and each chromosome replacement panel will be represented by a population of chromosome substitution strains using captured wild mice across China as chromosome donors. Given that chromosome 1 (Chr1) includes multiple gene loci related to lipid metabolism, we first screened Chr1 substitution strains to search for more appropriate mice model for MASLD research.