Efficient protocols and methods for high‐throughput utilization of the Collaborative Cross mouse model for dissecting the genetic basis of complex traits

Abstract

The Collaborative Cross (CC) mouse model is a next‐generation mouse genetic reference population (GRP) designated for a high‐resolution quantitative trait loci (QTL) mapping of complex traits during health and disease. The CC lines were generated from reciprocal crosses of eight divergent mouse founder strains composed of five classical and three wild‐derived strains. Complex traits are defined to be controlled by variations within multiple genes and the gene/environment interactions. In this article, we introduce and present variety of protocols and results of studying the host response to infectious and chronic diseases, including type 2 diabetes and metabolic diseases, body composition, immune response, colorectal cancer, susceptibility to Aspergillus fumigatus, Klebsiella pneumoniae, Pseudomonas aeruginosa, sepsis, and mixed infections of Porphyromonas gingivalis and Fusobacterium nucleatum, which were conducted at our laboratory using the CC mouse population. These traits are observed at multiple levels of the body systems, including metabolism, body weight, immune profile, susceptibility or resistance to the development and progress of infectious or chronic diseases. Herein, we present full protocols and step‐by‐step methods, implemented in our laboratory for the phenotypic and genotypic characterization of the different CC lines, mapping the gene underlying the host response to these infections and chronic diseases. The CC mouse model is a unique and powerful GRP for dissecting the host genetic architectures underlying complex traits, including chronic and infectious diseases.

Recombinant Inbred Mice as Models for Experimental Precision Medicine and Biology

“…The drawbacks of the BXDs are lower precision, and a decreased amount of variation in the population compared to e.g. multiparent families (such as the Collaborative Cross and the Diversity Outbred), and a consequent decrease in the total phenotypic variance [181]. We consider this an acceptable drawback, as we have shown that medically relevant phenotypes have variation in the family and it is possible to achieve subcentimorgan mapping precision using only half of the full set of strains [82].…”

Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

“… 5 The GD mice have a clear genetic background and are more genetically diverse than the commonly used inbred mice. Extensive research has been conducted on complex trait regulation and disease susceptibility, 6 , 7 treatment susceptibility, 8 , 9 prognosis prediction, 10 and toxicology 11 of complex diseases in GD mice, demonstrating the advantages of GD mice in terms of simulated genetic diversity.…”