eprintid: 1443059
rev_number: 46
eprint_status: archive
userid: 608
dir: disk0/01/44/30/59
datestamp: 2014-08-25 18:49:49
lastmod: 2021-10-04 01:45:39
status_changed: 2015-05-05 11:32:37
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Taylor, R
creators_name: Bullen, A
creators_name: Johnson, SL
creators_name: Grimm-Günter, EM
creators_name: Rivero, F
creators_name: Marcotti, W
creators_name: Forge, A
creators_name: Daudet, N
title: Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D06
note: © The Author 2014. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/),
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
abstract: Hearing relies on the mechanosensory inner and outer hair cells of the organ of Corti, which convert mechanical deflections of their actin-rich stereociliary bundles into electrochemical signals. Several actin-associated proteins are essential for stereocilia formation and maintenance, and their absence leads to deafness. One of the most abundant actin-bundling proteins of stereocilia is plastin 1, but its function has never been directly assessed. Here, we found that plastin 1 knock-out (Pls1 KO) mice have a moderate and progressive form of hearing loss across all frequencies. Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length. The stereocilia of outer hair cells were comparatively less affected, however they also showed signs of degeneration in ageing mice. The hair bundle stiffness and the acquisition of the electrophysiological properties of hair cells were unaffected by the absence of plastin 1, except for a significant change in the adaptation properties, but not the size, of the mechanoelectrical transducer currents. These results show that in contrast to other actin-bundling proteins such as espin, harmonin, or Eps8, plastin 1 is dispensable for the initial formation of stereocilia. However the progressive hearing loss and morphological defects of hair cells in adult Pls1 KO mice point at a specific role for plastin 1 in the preservation of adult stereocilia and optimal hearing. Hence, mutations in the human PLS1 gene may be associated to relatively mild and progressive forms of hearing loss.
date: 2014-08-14
official_url: http://dx.doi.org/10.1093/hmg/ddu417
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: JOURNAL ARTICLE
verified: verified_manual
elements_source: PubMed
elements_id: 971587
doi: 10.1093/hmg/ddu417
pii: ddu417
language_elements: ENG
lyricists_name: Bullen, Anwen
lyricists_name: Daudet, Nicolas
lyricists_name: Forge, Andrew
lyricists_name: Taylor, Ruth
lyricists_id: AABUL90
lyricists_id: NDAUD53
lyricists_id: AFORG20
lyricists_id: RRTAY12
full_text_status: public
publication: Human Molecular Genetics
volume: 24
number: 1
pagerange: 37-49
issn: 0964-6906
citation:        Taylor, R;    Bullen, A;    Johnson, SL;    Grimm-Günter, EM;    Rivero, F;    Marcotti, W;    Forge, A;           Taylor, R;  Bullen, A;  Johnson, SL;  Grimm-Günter, EM;  Rivero, F;  Marcotti, W;  Forge, A;  Daudet, N;   - view fewer <#>    (2014)    Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.                   Human Molecular Genetics , 24  (1)   pp. 37-49.    10.1093/hmg/ddu417 <https://doi.org/10.1093/hmg%2Fddu417>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1443059/2/Absence_of_plastin_1_causes_abnormal_maintenance_of_hair_cell_stereocilia_and_a_moderate_form_of_hearing_loss_in_mice..pdf