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Query: UMLS:C0344329 (
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28,634
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Auditory neuropathy 1 (AUNA1) is a form of human deafness resulting from a point mutation in the 5' untranslated region of the
Diaphanous homolog 3
(
DIAPH3
) gene. Notably, the
DIAPH3
mutation leads to the overexpression of the DIAPH3 protein, a formin family member involved in cytoskeleton dynamics. Through study of
diap3
-overexpressing transgenic (Tg) mice, we examine in further detail the anatomical, functional, and molecular mechanisms underlying AUNA1. We identify
diap3
as a component of the hair cells apical pole in wild-type mice. In the
diap3
-overexpressing Tg mice, which show a progressive threshold shift associated with a defect in inner hair cells (IHCs), the neurotransmitter release and potassium conductances are not affected. Strikingly, the overexpression of
diap3
results in a selective and early-onset alteration of the IHC cuticular plate. Molecular dissection of the apical components revealed that the microtubule meshwork first undergoes aberrant targeting into the cuticular plate of Tg IHCs, followed by
collapse
of the stereociliary bundle, with eventual loss of the IHC capacity to transmit incoming auditory stimuli.
...
PMID:Remodeling of the Inner Hair Cell Microtubule Meshwork in a Mouse Model of Auditory Neuropathy AUNA1. 2805 71
