Analysis of the Ush2a Gene in Medaka Fish (Oryzias latipes)

Elena Aller mail,
Ana V. Sánchez-Sánchez,
Javier U. Chicote,
Gema García-García,
Patricia Udaondo,
Laura Cavallé,
Marina Piquer-Gil,
Antonio García-España,
Manuel Díaz-Llopis,
José M. Millán,
José L. Mullor mail

Abstract

Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for genetic-based studies in biomedical research, we investigated the expression and function of the USH2A ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons, containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed during early stages of medaka fish development and persists into adulthood. Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization (WMISH) on embryos at different embryonic stages showed restricted expression to otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the development and/or maintenance of retinal photoreceptors and cochlear hair cells. Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects (small eyes and heads, otolith malformations and shortened bodies with curved tails) resulting in late embryo lethality. These embryonic defects, observed in our study and in other ciliary disorders, are associated with defective cell movement specifically implicated in left-right (LR) axis determination and planar cell polarity (PCP).

Citation: Aller E, Sánchez-Sánchez AV, Chicote JU, García-García G, Udaondo P, et al. (2013) Analysis of the Ush2a Gene in Medaka Fish (Oryzias latipes). PLoS ONE 8(9): e74995. doi:10.1371/journal.pone.0074995

Editor: Filippo Del Bene, Institut Curie, France

Received: November 16, 2012; Accepted: August 13, 2013; Published: September 23, 2013

Copyright: © 2013 Aller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by grants from the “Conselleria de Sanitat de la Comunitat Valenciana” (GE-011/10) and from the “Fondo de Investigaciones Sanitarias, FIS” (PI10/01825) and Ministerio de Economía y Competitividad BFU2009-10808. The authors would like to thank MICINN (Spain) for financial support (Projects CONSOLIDER INGENIO CSD-2010-00065). AGE is supported by the Research Stabilization Program of the Instituto de Salud Carlos III-Institut Catala de la Salut in Catalonia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.