Neuronal nicotinic receptors: Insights gained from gene knockout and knockin mutant mice

J. Drago*, C. D. McColl, M. K. Horne, D. I. Finkelstein, S. A. Ross

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    63 Citations (Scopus)

    Abstract

    Neuronal nicotinic acetylcholine receptors are ligand-gated ion channels that subserve a range of functions in the brain and peripheral nervous system. They are pentamers variously composed of a (a2-at0) and/3 subunits (β24). Pharmacological and ligand-binding studies have shown that the different subunits vary in their distribution and channel properties, but precise delineation of the in vivo function of individual subunits has been hampered by lack of subunit-specific antagonists. The development of transgenic mice with targeted deletions of specific subunits (knockout mice) or mutations in critical receptor domains (knockin mice) has extended understanding of nicotinic receptors, revealing that some subunits are necessary for viability, whereas others mediate modulatory effects on learning and memory, locomotion, anxiety, nociception, dopaminergic neurotransmission, seizure threshold, development of the visual system and autonomic function. In some cases, studies of transgenic mice have confirmed expectations derived from pharmacological and expression studies, but in other cases, compensation by related subunits has revealed a degree of functional redundancy not predicted by previous approaches.

    Original languageEnglish
    Pages (from-to)1267-1280
    Number of pages14
    JournalCellular and Molecular Life Sciences
    Volume60
    Issue number7
    DOIs
    Publication statusPublished - 1 Jul 2003

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