Phenotype and genotype comparison of C57BL/6N substrains contributing to the International Mouse Phenotyping Consortium (IMPC)

Abstract

The International Mouse Phenotyping Consortium (IMPC) is a 10‐ year program to produce a null mutant mouse line for every gene in the mouse genome, generate comprehensive phenotype data for each, and provide all the resources to the scientific community. The chosen mouse strain is the C57BL/6N, however there are several substrains of this mouse including C57BL/6NCrl (NCrl), C57BL/6NTac (NTac), and C57BL/6NJ (NJ). A C57BL/6Nderived embryonic stem (ES) cell line (JM8) was used to create the gene‐targeted clones. Given the scope of the IMPC project, it is important to catalog phenotype and genotype similarities or differences between the C57BL/6N substrains and ES cells used by the various IMPC centers. Here we describe results from genotype analyses using the Affymetrix Mouse Diversity Genotyping array to compare single‐nucleotide polymorphisms (SNP) between NCrl and NTac mice, and JM8 and C2 ES cell lines. In addition, whole genome sequencing (WGS) was carried out on NCrl, NTac, NJ, and JM8 genomic DNA. Phenotype analyses using the IMPC pipeline was conducted on NCrl and NTac mice at two separate locations; The Toronto Centre for Phenogenomics (TCP) and the Institut Clinique de la Souris (ICS). Substrain differences in certain traits were detected and the number of differences was strongly influenced by the rearing environment of the cohort, with fewer differences between NCrl and NTac cohorts derived from animals born and raised within the same institution.