Absence of Embigin accelerates hearing loss and causes sub-viability, brain and heart defects in C57BL/6N mice due to interaction with Cdh23^ahl

Mouse studies continue to help elaborate upon the genetic landscape of mammalian disease and the underlying molecular mechanisms. Here, we have investigated an Embigin^tm1b allele maintained on a standard C57BL/6N background and on a co-isogenic C57BL/6N background in which the Cdh23^ahl allele has been “repaired.” The hypomorphic Cdh23^ahl allele is present in several commonly used inbred mouse strains, predisposing them to progressive hearing loss, starting in high-frequency regions. Absence of the neural cell adhesion molecule Embigin on the standard C57BL/6N background leads to accelerated hearing loss and causes sub-viability, brain and cardiac defects. Contrastingly, Embigin^tm1b/tm1b mice maintained on the co-isogenic “repaired” C57BL/6N background exhibit normal hearing and viability. Thus Embigin genetically interacts with Cdh23. Importantly, our study is the first to demonstrate an effect of the common Cdh23^ahl allele outside of the auditory system, which has important ramifications for genetic studies involving inbred strains carrying this allele.