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Differential amplification of intron-containing transcripts reveals long term potentiation-associated up-regulation of specific Pde10A phosphodiesterase splice variants

Record type: Article

We employed differential display of expressed mRNAs (Liang, P., and Pardee, A. B. (1992) Science 257, 967–971) to identify genes up-regulated after long term potentiation (LTP) induction in the hippocampus of awake adult rats. In situ hybridization confirmed the differential expression of five independently amplified clones representing two distinct transcripts, cl13/19/90 and cl95/96. Neither cl13/19/90 nor cl95/96 showed significant sequence homology to known transcripts (mRNA or expressed sequence tag) or to the mouse or human genome. However, comparison with the rat genome revealed that they are localized to a predicted intron of the phosphodiesterase Pde10A gene. cl13/19/90 and cl95/96 are likely to be part of the Pde10A primary transcript as, using reverse transcriptase-PCR, we could specifically amplify distinct introns of the Pde10A primary transcript, and in situ hybridization demonstrated that a subset of Pde10A splice variants are also up-regulated after LTP induction. These results indicate that amplification of a primary transcript can faithfully report gene activity and that differential display can be used to identify differential expression of RNA species other than mRNA. In transiently transfected Cos7 cells, Pde10A3 reduces the atrial natriuretic peptide-induced elevation in cGMP levels without affecting basal cGMP levels. This cellular function of LTP-associated Pde10A transcripts argues for a role of the cGMP/cGMP-dependent kinase pathway in long term synaptic plasticity.

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Citation

O'Connor, Vincent, Genin, Alexis, Davis, Sabrina, Karishma, K.K., Doyère, Valerie, De Zeeuw, Chris I., Sanger, Gareth, Hunt, Stephen P., Richter-Levin, Gal, Mallet, Jaques, Laroche, Serge, Bliss, T.V.P. and French, Pim J. (2004) Differential amplification of intron-containing transcripts reveals long term potentiation-associated up-regulation of specific Pde10A phosphodiesterase splice variants The Journal of Biological Chemistry, 279, (16), pp. 15841-15849. (doi:10.1074/jbc.M312500200).

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Published date: 16 April 2004

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Local EPrints ID: 24575
URI: http://eprints.soton.ac.uk/id/eprint/24575
ISSN: 0021-9258
PURE UUID: b9b041e9-8295-438f-8dae-a02eee295592

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Date deposited: 05 Apr 2006
Last modified: 17 Jul 2017 16:13

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Contributors

Author: Alexis Genin
Author: Sabrina Davis
Author: K.K. Karishma
Author: Valerie Doyère
Author: Chris I. De Zeeuw
Author: Gareth Sanger
Author: Stephen P. Hunt
Author: Gal Richter-Levin
Author: Jaques Mallet
Author: Serge Laroche
Author: T.V.P. Bliss
Author: Pim J. French

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