Journal article
A Comparative Study of Eya1 and Eya4 Protein Function and Its Implication in Branchio-oto-renal Syndrome and DFNA10
Journal of the Association for Research in Otolaryngology, Vol.5(3), pp.295-304
09/2004
DOI: 10.1007/s10162-004-4044-3
PMCID: PMC2504552
PMID: 15492887
Abstract
Allele variants of
EYA1
and
EYA4
, two members of the vertebrate
Eya
gene family, underlie two types of inherited human
deafness, branchio-oto-renal (BOR) syndrome and DFNA10, respectively. To clarify how
mutations in these two genes and their encoded proteins impact the normal biology of
hearing, we completed a number of functional studies using the yeast-two-hybrid
system. We verified that bait constructs of the homologous region (
Eya1HR
and
Eya4HR
)
interact with
Six1
prey constructs, although no
interaction with
Dach1
prey was demonstrable. To
compare interaction affinities, we evaluated α-galactosidase activity after
cotransformation of
Eya1HR/Six1
and
Eya4HR/Six1
and found that the latter interaction was
weaker. By immunofluorescence staining, we showed Eya4HR localization to the
cytoplasm. After coexpression of
Six1
, Eya4HR was
translocated to the nucleus. Results with Eya1HR were similar. Translation of mutant
constructs (
Eya4HR
R564X
and
Eya1HR
R539X
) could not be demonstrated. Using dual
Eya
-containing constructs (with two wild-type alleles or
wild-type and mutant alleles), we confirmed no translation of the mutant allele,
even if the mutation was nontruncating. These results are consistent with clinical
data and implicate haploinsufficiency as the cause of BOR syndrome and
DFNA10.
Details
- Title: Subtitle
- A Comparative Study of Eya1 and Eya4 Protein Function and Its Implication in Branchio-oto-renal Syndrome and DFNA10
- Creators
- Yuzhou Zhang - Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, IA 52242 USABoyd M Knosp - The University of Iowa ITS Research Service, University of Iowa, Iowa City, IA 52242 USAMark Maconochie - School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG UKRick A Friedman - House Ear Institute, Los Angeles, CA 90057 USARichard J.H Smith - Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Journal of the Association for Research in Otolaryngology, Vol.5(3), pp.295-304
- DOI
- 10.1007/s10162-004-4044-3
- PMID
- 15492887
- PMCID
- PMC2504552
- NLM abbreviation
- J Assoc Res Otolaryngol
- ISSN
- 1525-3961
- eISSN
- 1438-7573
- Publisher
- Springer-Verlag; New York
- Language
- English
- Date published
- 09/2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medicine Administration; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006406002771
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