PT  - JOURNAL ARTICLE
AU  - Clément Surel
AU  - Marie Guillet
AU  - Marc Lenoir
AU  - Jérôme Bourien
AU  - Gaston Sendin
AU  - Willy Joly
AU  - Benjamin Delprat
AU  - Marci M. Lesperance
AU  - Jean-Luc Puel
AU  - Régis Nouvian
TI  - Remodeling of the Inner Hair Cell Microtubule Meshwork in a Mouse Model of Auditory Neuropathy AUNA1
AID  - 10.1523/ENEURO.0295-16.2016
DP  - 2016 Nov 01
TA  - eneuro
PG  - ENEURO.0295-16.2016
VI  - 3
IP  - 6
4099  - http://www.eneuro.org/content/3/6/ENEURO.0295-16.2016.short
4100  - http://www.eneuro.org/content/3/6/ENEURO.0295-16.2016.full
SO  - eNeuro2016 Nov 01; 3
AB  - 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.