GABA(A) receptors: gene expression and evolution

Pahal, I., 2005. GABA(A) receptors: gene expression and evolution. PhD, Nottingham Trent University.

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γ-Aminobutyric acid (GABA) is the principle inhibitory neurotransmitter in the vertebrate central nervous system. It binds to three classes of receptor, namely, the GABAA, GABAB and GABAc receptor. The GABAA receptor exists as a pentamer, formed by the association of different types of subunits (α1-α6, β1-β3, γ1-γS, δ, ϵ, π and 0). Two further subunits have been identified in the chicken namely the γ4 subunit (replacing the mammalian β1-subunit), and the γ4-subunit (replacing the mammalian γ3-subunit).

The aims of this project were to study the molecular evolution of GABAA receptor subunit genes, investigate changes in gene expression and search for a potential evolutionary cluster by in silico analysis. The former was carried out by cloning GABAA receptor β-subunit complementary DNAs (cDNAs) from various lower vertebrate species, and searching published genome databases for these genes. In situ hybridization experiments determined the distribution of the GABAA receptor β4-subunit mRNA in the one-day-old chick brain and the zebra finch brain (both -provide useful models of learning, namely, imprinting and song learning, respectively).

Unexpectedly four GABAA receptor subunit cDNAs were isolated from the zebra finch. In silico analysis of the puffer fish draft genome sequence also revealed the presence of four GABAA receptor β-subunit-like genes. The genome of sea squirt revealed a cluster of GABAA receptor α- and β-like and glycine receptor-like subunit genes, which are highly, conserved with vertebrate GABAA receptor genes both in gene structure and transcriptional orientation. The β4 subunit was present in other species e.g. common wall lizard and African clawed frog hence, not avian specific.

The subunit mRNA was detected in the medial striatum and the mesopallium, in adult and juvenile zebra finch brain, both areas that contain nuclei important for song production. The chicken genome revealed a cluster of GABAA receptor α3, β4 and γ4 subunit genes orthologous to the cluster of genes on the X chromosome in man. In the one-day-old chick brain, the distribution of this subunit mRNA appeared similar in some brain areas to that of the α3 and γ4-subunit mRNA, suggesting that these genes are coordinately regulated forming native receptor subtypes in some brain areas.

Item Type: Thesis
Creators: Pahal, I.
Date: 2005
ISBN: 9781369314496
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 18 Sep 2020 13:51
Last Modified: 27 Jul 2023 09:34

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