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CANCELLED: Hearing and Donuts (Brain and Bagels) Seminar
October 11, 2019 @ 8:30 am - 9:30 am
This event has been rescheduled for November 1, 2019.
Presenter: Robert Fettiplace, Ph.D., Professor, Neuroscience, UW Madison
Topic: Two TMC1 Mutations Cause Hair Cell Degeneration and Progressive Dominant Deafness
Transmembrane channel-like protein isoform 1 (TMC1) is thought to be a major component of the mechanoelectrical transducer channels in cochlear hair cells. We have characterized a novel Tmc1 mouse with a single amino acid mutation (D569N), which is homologous to a dominant human deafness mutation. By 30 days, Tmc1 pD569N heterozygote mice were profoundly deaf, and there was substantial loss of outer hair cells (OHCs). Mechanoelectrical transducer currents were still present in mutant OHCs but the transducer-channel Ca2+ permeability was reduced three-fold in Tmc1 pD569N homozygotes, intermediate deficits being seen in heterozygotes. The reduction in Ca2+ permeability resembled that of the Tmc1 pM412K Beethoven mutant, a previously-studied dominant mouse mutation. We show that, in contrast to the Tmc1 pM412K mutant, there was reduced expression of the TMC1 pD569N channel at the transduction site. The reduction in MET channel Ca2+ permeability seen in both mutants may be the proximate cause of hair-cell apoptosis.