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

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.

journal_name

Biol Cell

journal_title

Biology of the cell

authors

Li Y,Manaligod JM,Weeks DL

doi

10.1042/BC20090098

subject

Has Abstract

pub_date

2010-02-17 00:00:00

pages

277-92

issue

5

eissn

0248-4900

issn

1768-322X

pii

BC20090098

journal_volume

102

pub_type

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