CaltechAUTHORS
  A Caltech Library Service

Insights into the Neurobiology of the Nicotinic Cholinergic System and Nicotine Addiction from Mice Expressing Nicotinic Receptors Harboring Gain-of-Function Mutations

Drenan, Ryan M. and Lester, Henry A. (2012) Insights into the Neurobiology of the Nicotinic Cholinergic System and Nicotine Addiction from Mice Expressing Nicotinic Receptors Harboring Gain-of-Function Mutations. Pharmacological Reviews, 64 (4). pp. 869-879. ISSN 0031-6997. PMCID PMC3462994. doi:10.1124/pr.111.004671. https://resolver.caltech.edu/CaltechAUTHORS:20121108-131347078

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20121108-131347078

Abstract

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated, cation-selective ion channels expressed throughout the brain. Although these channels have been investigated for several decades, it is still challenging 1) to identify the important nAChR subunits in cholinergic transmission and nicotine dependence and 2) to develop nAChR subtype-specific ligands. To overcome these challenges, we and others have studied mice expressing mutant, gain-of-function nAChR subunits. In this review, we discuss this research approach and the results it has yielded to date. Gain-of-function mutations, including those in nAChR subunits, provide an approach that is complementary to loss-of-function studies such as gene knockouts; the former allows one to answer questions of sufficiency and the latter addresses questions of necessity. Mutant mice expressing gain-of-function nAChR subunits are commonly produced using traditional gene targeting in embryonic stem cells, but novel approaches such as bacterial artificial chromosome transgenesis have yielded important insights as well. α7 nAChRs were the first nAChRs to be targeted with a gain-of-function mutation, followed by a pair of α4 nAChR gain-of-function mutant mice. These α4 nAChR gain-of-function mice (α4 L9′S mice, followed by α4 L9′A mice) provided an important system to probe α4 nAChR function in vivo, particularly in the dopamine reward system. α6 nAChR gain-of-function mice provided the first robust system allowing specific manipulation of this receptor subtype. Other targeted mutations in various nAChR subunits have also been produced and have yielded important insights into nicotinic cholinergic biology. As nAChR research advances and more details associated with nAChR expression and function emerge, we expect that existing and new mouse lines expressing gain-of-function nAChR subunits will continue to provide new insights.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1124/pr.111.004671DOIArticle
http://pharmrev.aspetjournals.org/content/64/4/869PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462994/PubMed CentralArticle
ORCID:
AuthorORCID
Drenan, Ryan M.0000-0002-8141-8577
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2012 by The American Society for Pharmacology and Experimental Therapeutics. Published online before print August 10, 2012. This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grants DA030396, DA19335, DA17279]; the National Institutes of Health National Institute on Aging [Grant AG33954]; the National Institutes of Health National Institute of Mental Health [Grant MH86383]; and the University of California Tobacco Related Disease Research Program [Grant 17RT-0127]. Authorship Contributions: Wrote or contributed to the writing of the manuscript: Drenan and Lester.
Funders:
Funding AgencyGrant Number
NIHDA030396
NIHDA19335
NIHDA17279
NIHAG33954
NIHMH86383
California Tobacco-Related Disease Research Program17RT-0127
Issue or Number:4
PubMed Central ID:PMC3462994
DOI:10.1124/pr.111.004671
Record Number:CaltechAUTHORS:20121108-131347078
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20121108-131347078
Official Citation: Ryan M. Drenan and Henry A. Lester Insights into the Neurobiology of the Nicotinic Cholinergic System and Nicotine Addiction from Mice Expressing Nicotinic Receptors Harboring Gain-of-Function Mutations Pharmacol Rev October 2012 64:869-879; published ahead of print August 10, 2012, doi:10.1124/pr.111.004671
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35367
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Nov 2012 19:33
Last Modified:09 Nov 2021 23:14

Repository Staff Only: item control page