EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis

Youe Li; Jose M Manaligod; Daniel L Weeks

doi:10.1042/BC20090098

Back

EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis

Journal article

Open access

Peer reviewed

EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis

Youe Li, Jose M Manaligod and Daniel L Weeks

Biology of the cell, Vol.102(Pt 5), pp.277-292

05/2010

DOI: 10.1042/BC20090098

PMCID: PMC2825735

PMID: 19951260

Files and links (1)

url

https://doi.org/10.1042/BC20090098View

Published (Version of record) Open Access

Abstract

Background information . The BOR (branchio-oto-renal) syndrome is a dominant disorder most commonly caused by mutations in the EYA1 (Eyes Absent 1) gene. Symptoms commonly include deafness and renal anomalies. Results . We have used the embryos of the frog Xenopus laevis as an animal model for early ear development to examine the effects of different EYA1 mutations. Four eya1 mRNAs encoding proteins correlated with congenital anomalies in human were injected into early stage embryos. We show that the expression of mutations associated with BOR, even in the presence of normal levels of endogenous eya1 mRNA, leads to morphologically abnormal ear development as measured by overall otic vesicle size, establishment of sensory tissue and otic innervation. The molecular consequences of mutant eya1 expression were assessed by QPCR (quantitative PCR) analysis and in situ hybridization. Embryos expressing mutant eya1 showed altered levels of multiple genes ( six1 , dach , neuroD , ngnr-1 and nt3 ) important for normal ear development. Conclusions . These studies lend support to the hypothesis that dominant-negative effects of EYA1 mutations may have a role in the pathogenesis of BOR.

Xenopus

DIG, digoxigenin

branchio-oto-renal (BOR)

GFP, green fluorescent protein

THF, tetrahydrofuran

otic development

EYA1, Eyes Absent 1

HAD, haloacid dehalogenase

HRP, horseradish peroxidase

DACH, dachshund

QPCR, quantitative PCR

Eyes Absent 1 (EYA1) gene

RT–PCR, reverse transcription–PCR

six, sine oculis

DMED, dimethylethylenediamine

BOR, branchio-oto-renal

GST, glutathione transferase

disease model

spcd, spinal cord

Details

Title: Subtitle: EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis
Creators: Youe Li - Department of Otolaryngology, Carver College of Medicine, University of Iowa, Iowa City, IA, U.S.A
Jose M Manaligod - Department of Otolaryngology, Carver College of Medicine, University of Iowa, Iowa City, IA, U.S.A
Daniel L Weeks - †Department of Biochemistry, Carver College of Medicine, University of Iowa, University of Iowa, Iowa City, IA, U.S.A
Resource Type: Journal article
Publication Details: Biology of the cell, Vol.102(Pt 5), pp.277-292
Publisher: Portland Press Ltd
DOI: 10.1042/BC20090098
PMID: 19951260
PMCID: PMC2825735
ISSN: 0248-4900
eISSN: 1768-322X
Alternative title: Expression of EYA1 mutations in Xenopus embryos
Language: English
Date published: 05/2010
Academic Unit: Stead Family Department of Pediatrics; Biochemistry and Molecular Biology; Otolaryngology
Record Identifier: 9984006429602771

Metrics

27 Record Views

29 Times Cited - Web of Science