Naturally occurring genetic variability in the nicotinic acetylcholine receptor alpha4 and alpha7 subunit genes and phenotypic diversity in humans and mice.

Through the use of pharmacological and molecular strategies, the identities of the nicotinic acetylcholine receptor (nAChR) subtypes that modulate different behaviors and physiological measures are being revealed. However, little is known with respect to how naturally occurring genetic variability in the genes that encode the members of the neuronal nAChR family contribute to phenotypic diversity in humans and research organisms. Because behavior, physiology and disease susceptibility in humans and other species are influenced to some extent by genetic factors and nAChRs contribute to a wide range of phenotypes, it is likely that polymorphisms in the genes that encode the nAChR subunit family contribute to phenotypic variability among individuals in a population. Over the past decade, data have accumulated that support the premise that naturally occurring nAChR subunit gene variability contributes to phenotypic diversity in both humans and mice. In this review, current evidence for the role of variability in the genes that encode the two major brain-expressed alpha subunits, alpha4 and alpha7, in modulating behavior, physiology and disease risk in both humans and mice will be discussed.