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A novel splice variant of the glycine receptor alpha2 subunit is dramatically downregulated during prenatal development



A novel splice variant of the glycine receptor alpha2 subunit is dramatically downregulated during prenatal development



Society for Neuroscience Abstracts 26(1-2): Abstract No -695 17



Several lines of evidence indicate that the expression of inhibitory glycine receptors (GlyRs) undergoes developmental regulation, with alpha2 subunits most abundant at pre- and neonatal stages, and alpha1 subunits predominating in adults. However, assays of GlyR alpha-subunit mRNA using the RT-PCR method show that these developmental changes are not absolute. That is, alpha1 mRNA is present in the spinal cord as early as E14, and alpha2 mRNA is still present in the adult. We performed experiments to compare the relative amounts of mRNA for two previously described splice variants of the alpha2 subunit, alpha2A and alpha2B, in the rat spinal cord at different stages of development. RT-PCR followed by restriction analysis showed that the alpha2A isoform was by far the predominant isoform at all stages examined. However, these experiments revealed the existence of an additional, novel splice variant of the alpha2 subunit, one that is missing exon 3; we have termed this novel splice variant "alpha2N." Examination of the spinal cords of different-aged rats indicated that this novel splice variant undergoes dramatic down-regulation during prenatal development, with its mRNA forming a significant portion of the alpha2 subunit pool at E14, but being undetectable a few days later, at the time of birth. Initial examination of spinal cord cultures has suggested that alpha2N undergoes striking down-regulation over about the first week culture, as well. These results provide evidence for a novel splice variant of the GlyR alpha2 subunit that undergoes the most dramatic developmental regulation of any GlyR subunit to date.

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Accession: 034312233

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