The Squeaky Wheel

Despite recent progress in identifying genes underlying deafness, there are still relatively few mouse models of specific forms of human deafness. Here we describe the phenotype of the Beethoven (Bth) mouse mutant and a missense mutation in Tmc1 (transmembrane cochlear-expressed gene 1). Progressive hearing loss (DFNA36) and profound congenital deafness (DFNB7/B11) are caused by dominant and recessive mutations of the human ortholog, TMC1 (ref. 1), for which Bth and deafness (dn) are mouse models, respectively.

From S. Vreugde et al., “Beethoven, a mouse model for dominant, progressive hearing loss DFNA36," Nature Genetics vol. 30, no. 3 (2002). The significance is that both the Bth mutation, which the authors describe, and the previously discovered dn mutation occur on the same gene (Tmc1), which has a known human homologue (TMC1). In other words, the degeneration of cochlear hair cells, which leads to the gradual onset of certain kinds of deafness, has a genetic basis that can be modeled in the lab. “Beethoven," the authors conclude, “may thus provide insight into the factors needed for long-term survival of hair cells and may increase our understanding of the hair-cell degeneration assumed to be associated with progressive hearing loss with ageing (presbyacusis) in a large proportion of the human population."