Functional Studies of 'Deafness Genes' Essential for Hearing

Friedman, Thomas

Abstract

In addition to completing projects on MYO15 involving its function in stereocilia development, we continue to pursue studies of mouse models of human deafness genes that have been identified in the LMG. At least two of the three major isoforms of TRIOBP (TRIOBP-4 and TRIOBP-5) are necessary for normal hair cell stereocilia rootlet formation and the maintenance of stereocilia rootlets in the adult organ of Corti. Rootlets provide bundle stiffness necessary for the detection of sound. The function of TRIOBP-1, if any, in the auditory system has not been examined. TRIOBP-1 is necessary for embryonic development. A body-wide ablation of expression of TRIOBP-1 is lethal during development. To understand the function of TRIOBP-1 in the auditory system we have developed a floxed allele of a unique exon of the TRIOBP-1 isoform and will delete TRIOBP-1 expression just in the auditory system using appropriate cre-expressors. Similar strategies will be used to study the function of several other genes necessary for hearing.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Deafness and Other Communication Disorders (NIDCD)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIADC000048-22
• Application #: 10003739
• Support Year: 22
• Fiscal Year: 2019

Institution

• Name: National Institute on Deafness and Other Communication Disorders

Publications

Dewey, James B; Xia, Anping; Müller, Ulrich et al. (2018) Mammalian Auditory Hair Cell Bundle Stiffness Affects Frequency Tuning by Increasing Coupling along the Length of the Cochlea. Cell Rep 23:2915-2927

Ballesteros, Angela; Fenollar-Ferrer, Cristina; Swartz, Kenton Jon (2018) Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins. Elife 7:

Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J et al. (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780-798

Melli, Luca; Billington, Neil; Sun, Sara A et al. (2018) Bipolar filaments of human nonmuscle myosin 2-A and 2-B have distinct motile and mechanical properties. Elife 7:

Faridi, R; Rehman, A U; Morell, R J et al. (2017) Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome. Clin Genet 91:328-332

Bird, Jonathan E; Barzik, Melanie; Drummond, Meghan C et al. (2017) Harnessing molecular motors for nanoscale pulldown in live cells. Mol Biol Cell 28:463-475

Mauriac, Stephanie A; Hien, Yeri E; Bird, Jonathan E et al. (2017) Defective Gpsm2/G?i3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome. Nat Commun 8:14907

Naz, Sadaf; Imtiaz, Ayesha; Mujtaba, Ghulam et al. (2017) Genetic causes of moderate to severe hearing loss point to modifiers. Clin Genet 91:589-598

Rehman, A U; Friedman, T B; Griffith, A J (2017) Unresolved questions regarding human hereditary deafness. Oral Dis 23:551-558

Belyantseva, Inna A (2016) Helios(®) Gene Gun-Mediated Transfection of the Inner Ear Sensory Epithelium: Recent Updates. Methods Mol Biol 1427:3-26