Knockout of ush2a gene in zebrafish causes hearing impairment and late onset rod-cone dystrophy

Human Genetics
Shanshan HanMugen Liu

Abstract

Most cases of Usher syndrome type II (USH2) are due to mutations in the USH2A gene. There are no effective treatments or ideal animal models for this disease, and the pathological mechanisms of USH2 caused by USH2A mutations are still unknown. Here, we constructed a ush2a knockout (ush2a-/-) zebrafish model using TALEN technology to investigate the molecular pathology of USH2. An early onset auditory disorder and abnormal morphology of inner ear stereocilia were identified in the ush2a-/- zebrafish. Consequently, the disruption of Ush2a in zebrafish led to a hearing impairment, like that in mammals. Electroretinography (ERG) test indicated that deletion of Ush2a affected visual function at an early stage, and histological analysis revealed that the photoreceptors progressively degenerated. Rod degeneration occurred prior to cone degeneration in ush2a-/- zebrafish, which is consistent with the classical description of the progression of retinitis pigmentosa (RP). Destruction of the outer segments (OSs) of rods led to the down-regulation of phototransduction cascade proteins at late stage. The expression of Ush1b and Ush1c was up-regulated when Ush2a was null. We also found that disruption of fibronectin assembly at the retinal b...Continue Reading

References

Jan 1, 1974·Developmental Psychobiology·C B KimmelR O Kimmel
Jan 1, 1983·Journal of Chronic Diseases·J A BoughmanK A Shaver
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·T HassonM S Mooseker
Mar 1, 1994·American Journal of Medical Genetics·R J SmithL Tranebjaerg
Jun 19, 1996·Annals of the New York Academy of Sciences·M Fetter, J Dichgans
Aug 1, 1996·Trends in Neurosciences·E Newman, A Reichenbach
Jul 26, 2000·European Journal of Human Genetics : EJHG·B DreyerO Nilssen
Nov 10, 2001·Annual Review of Genomics and Human Genetics·C Petit
Dec 19, 2001·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J BilottaS E Sutherland
Feb 12, 2002·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Stephen J MoormanSarah A Davies
Mar 17, 2004·Journal of Neuroscience Methods·Yuri V MakhankovStephan C F Neuhauss
Jun 24, 2004·Nature Reviews. Genetics·Gregory I FrolenkovAndrew J Griffith
Dec 14, 2004·Human Molecular Genetics·Avital AdatoChristine Petit
Mar 23, 2005·The Journal of Experimental Biology·David G Zeddies, Richard R Fay
May 3, 2006·The Laryngoscope·Ronald J E PenningsEmmanuel A M Mylanus
Jun 16, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joann McGeeGuy P Richardson
Nov 23, 2006·Lancet·Dyonne T HartongThaddeus P Dryja
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Xiaoqing LiuTiansen Li
Jun 15, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nicolas MichalskiChristine Petit
Apr 9, 2008·International Journal of Pediatric Otorhinolaryngology·Xue Z LiuThomas J Balkany
Jun 6, 2008·American Journal of Physiology. Cell Physiology·Lauren L DanieleNancy J Philp
Jan 27, 2009·Current Opinion in Neurology·Zubin SaihanMaria Bitner-Glindzicz
Dec 5, 2009·Investigative Ophthalmology & Visual Science·Bin LuRaymond D Lund
Sep 8, 2010·BMC Neuroscience·Weike MoTeresa Nicolson
Jan 1, 2008·CSH Protocols·Valerie C FleischStephan C F Neuhauss
Dec 23, 2011·Investigative Ophthalmology & Visual Science·Muhammad Asif NaeemS Amer Riazuddin
May 17, 2012·Biochimica Et Biophysica Acta·Xiukun CuiMugen Liu
Oct 10, 2012·The Journal of Cell Biology·Iman SahlyChristine Petit
Nov 22, 2012·Nature Reviews. Molecular Cell Biology·J Keith Joung, Jeffry D Sander
Feb 22, 2014·Methods : a Companion to Methods in Enzymology·Yun LiuChristopher H K Cheng
Dec 8, 2014·Biochimica Et Biophysica Acta·Pranav Mathur, Jun Yang

❮ Previous
Next ❯

Citations

Jan 31, 2020·Human Molecular Genetics·Maria TomsMariya Moosajee
Aug 1, 2020·Frontiers in Cellular Neuroscience·Lucy S FrenchLivia S Carvalho
Jan 14, 2021·Biomolecules·Nicole C L NoelW Ted Allison
Nov 17, 2020·Frontiers in Genetics·Meg WhatleyElaine Y M Wong
May 1, 2021·International Journal of Molecular Sciences·Evan M de JoyaXuezhong Liu
Jul 3, 2021·International Journal of Molecular Sciences·Carla Fuster-GarcíaGema García-García
Oct 19, 2019·Chemical Research in Toxicology·Steven CassarLeonard I Zon
Mar 23, 2020·Hearing Research·Gwenaelle G S Géléoc, Aziz El-Amraoui
Sep 30, 2021·International Ophthalmology Clinics·Astra DinculescuDavid A Saperstein
Oct 31, 2020·Experimental Eye Research·Lyes ToualbiMariya Moosajee

❮ Previous
Next ❯

Methods Mentioned

BETA
gene knockout
in vitro transcription
PCR
transmission electron microscopy
delamination
SANS

Software Mentioned

Quantity One
MATLAB

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.