Detection of cone alpha transducin mRNA in human fetal cochlea: negative mutation analysis in Usher syndrome

doi:10.1016/S0378-5955(96)00073-1

Hearing Research

Volume 99, Issues 1–2, 15 September 1996, Pages 7-12

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Abstract

Cone alpha transducin (GNAT2), known to be expressed in photoreceptors, was found to be transcribed in human fetal cochlea. Due to the unexpected finding of expression of this gene in the inner ear and the success of the candidate gene approach in identifying mutations for a variety of heritable disorders, we investigated the possible role of this gene in Usher syndrome type I and type II. Single-strand conformation polymorphism (SSCP) was used to screen the GNAT2 coding region, as well as splice donor and acceptor sites, for mutations in a total of 140 unrelated patients. Two nucleotide changes leading to two silent amino acid changes and one rare polymorphism were found. In view of these results and those of a previously published Southern blot analysis, it is unlikely that mutations in GNAT2 are a common gene abnormality in Usher syndrome type I or type II.

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Characterization of G-protein βγ expression in the inner ear
1999, Molecular Brain Research
Heterotrimeric guanine nucleotide binding proteins (G-proteins) are composed of a diverse set of α, β, and γ subunits, which couple cell surface receptors to intracellular effectors, such as adenylyl cyclase, phospholipase Cβ, and ion channels. Both the Gα and the Gβγ dimers mediate effector activity and are believed to contribute to the complexity of the signaling pathway. Molecular and immunocytochemical techniques were employed to determine diversity of Gβ and Gγ subunit expression in the murine inner ear. PCR-based assessment of λZAP unidirectional cDNA libraries, representing the cochlea and inner ear hair cells, indicated all five known Gβ subunits were present in the cochlea, while only a subset of Gγ isoforms were found. New or novel G-protein β and γ subunits were not detected. cDNAs representing Gβ1-4 and Gγ2, Gγ3, Gγ5, Gγ8_olf subunit transcripts were isolated. In addition, cDNAs corresponding to the Gβ5 and Gγ11 isoforms exhibited restricted expression to inner and outer hair cells, respectively. Antisera specific for Gβ3, Gβ4, Gγ3, Gγ5 and Gγ11 stained spiral ganglion and neurosensory hair cells. A unique finding was the variable topological distribution of Gγ3 in the spiral ganglion cells along the cochlear axis. Collectively, our results demonstrate a complementary as well as differential distribution pattern for Gβ and Gγ isoforms exists in the inner ear. The co-localization of various G-protein isoforms within the same cell type suggests specific combinatorial Gβ and Gγ subunit associations may preferentially be formed. Thus, the detection of multiple subunits presumably reflects the extent of the functional diversity of inner ear signaling pathways and should provide specificity of G-protein mediated pathways.
Mapping of a novel locus for achromatopsia (ACHM4) to 1 p and identification of a germline mutation in the α subunit of cone transducin (GNAT2)
2002, Journal of Medical Genetics

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Research paperDetection of cone alpha transducin mRNA in human fetal cochlea: negative mutation analysis in Usher syndrome

Abstract

Am. J. Ophthalmol.

Genomics

Genomics

Genomics

Genomics

Hear. Res.

Genomics

Hear. Res.

Increased incidence of abnormal nasal cilia in patients with retinitis pigmentosa

Nature

Ultrastructure of connecting cilia in different forms of retinitis pigmentosa

Arch. Ophthalmol.

Molecular mechanism of visual transduction

Eur. J. Biochem.

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

Detection of point mutations in the p53 gene: Comparison of single-strand conformation polymorphism, constant denaturant gel electrophoresis, and hydroxylamine and osmium tetroxide techniques

Hum. Mutat.

Nasal cilia in retinitis pigmentosa

Usher's syndrome: ophthalmic and neurologic findings suggesting genetic heterogeneity

Arch. Ophthalmol.

Flow of information in the light-triggered cyclic nucleotide cascade of vision

Retinitis pigmentosa combined with congenital deafness with vestibulo-cerebellar ataxia and mental abnormality in a proportion of cases: a clinical and geneticostatistical study

Acta. Psychiatr. Scand. Suppl.

Abnormal sperm and photoreceptor axonemes in Usher's syndrome

Arch. Ophthalmol.

Research paper
Detection of cone alpha transducin mRNA in human fetal cochlea: negative mutation analysis in Usher syndrome