The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells

Recessive mutations in myosin 15, a class XV unconventional myosin, cause p rofound congenital deafness in humans and both deafness and vestibular dysf unction in mice homozygous for the shaker 2 and shaker 2(J) alleles, The sh aker 2 allele is a previously described missense mutation of a highly conse rved residue in the motor domain of myosin XV, The shaker 2(J) lesion, in c ontrast, is a 14.7 kb deletion that removes the last six exons from the 3'- terminus of the Myo 15 transcript, These exons encode a FERM (F, ezrin, rad ixin and moesin) domain that may interact with integral membrane proteins, Despite the deletion of six exons, Myo15 mRNA transcripts and protein are p resent in the post-natal day 1 shaker 2(J) inner ear, which suggests that t he FERM domain is critical for the development of normal hearing and balanc e, Myo15 transcripts are first detectable at embryonic day 13.5 in wild-typ e mice, Myo15 transcripts in the mouse inner ear are restricted to the sens ory epithelium of the developing cristae ampularis, macula utriculi and mac ula sacculi of the vestibular system as well as to the developing organ of Corti, Both the shaker 2 and shaker 2(J) alleles result in abnormally short hair cell stereocilia in the cochlear and vestibular systems, This suggest s that Myo15 may be important for both the structure and function of these sensory epithelia.