C57BL/6-derived mice and the Cdh23^ahl allele - Background matters

C57BL/6-derived mice are the most utilised mice in biomedical research, and yet actually there is no such thing as a generic C57BL/6 mouse. Instead, there are more than 150 C57BL/6-derived sub-strains recognised by the Mouse Genome Informatics (MGI) database, each of which carry sub-strain-specific fixed genetic differences that can potentially lead to phenotypic differences affecting a single, or multiple biological systems. One of the most widely known strain-specific alleles is the Cdh23^ahl allele, a single nucleotide change that predisposes C57BL/6-derived mice to a progressive hearing loss that starts in the high-frequency region. As such, this allele is of particular relevance to auditory researchers. However, a recent study, comparing C57BL/6NTac mice with a co-isogenic strain in which the Cdh23^ahl allele has been 'repaired' using genome editing, suggests that the Cdh23^ahl allele may have a broader effect on phenotype expressivity of mouse mutants impacting not just the auditory system, but other organ systems as well. Here, using the Cdh23^ahl allele as an exemplar, we discuss the importance of knowing, understanding and reporting the genetic background of mouse mutants.