Functional Studies of "Deafness Genes" Essential for Hearing

National Institute On Deafness And Other Communication Disorders

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Abstract

LMG, NIDCD/NIH staff are continuing to pursue studies of mouse models of human deafness genes that were identified in the LMG. At least two of the three major isoforms of TRIOBP (TRIOBP-4 and TRIOBP-5, identified from our previous published studies of human nonsyndromic autosomal recessive deafness) are necessary for normal hair cell stereocilia rootlet formation and the maintenance of rootlets in the adult organ of Corti. Stereocilia rootlets provide bundle stiffness necessary for the detection of sound and, yet paradoxically, rootlets must also be flexibie at stereocilia pivot points, which is the topic of a paper recently published (Belyantseva and Chang et al 2025, JCB). The function of TRIOBP-1, the third major TRIOBP alternative isoform, if any, in the auditory system has not been reported and is being examined using a floxed exon 1 unique (i.e. not used in transcripts of Triobp-4 and Triobp-5 splice isoforms) to the Triobp 1 isofrom. Similar experimental strategies are being used to study in mouse the functions of other genes we know are necessary for hearing in human that we have identified from genetic analyses of large families segregating deafness. These newly discovered "deafness genes" presently include LRP2, MAP3K1, GPN2 and ADAMTS.