Clinical implications from studies of α1 adrenergic receptor knockout mice

alpha 1-Adrenergic receptors (alpha 1-ARs) modulate a large number of physiological functions in cardiovascular and noncardiovascular tissues. Because individual members of the alpha 1-AR family (alpha 1A-, alpha 1B-, and alpha 1D-ARs) have overlapping expression profiles in most tissues, elucidation of the precise physiological roles of individual alpha 1-AR subtypes remains a challenging task. To alleviate this constraint, a gene targeting approach has been employed to generate mutant mice lacking one or two alpha 1-AR genes. Recent studies on these mutant mouse strains are discussed in this article, with an emphasis on the role of alpha 1-AR in the central nervous system and lower urinary tracts. These are two major tissues of particular interest for the development of new therapeutic strategies targeted to the alpha 1-ARs. By combining gene targeting techniques with pharmacological tools, the specific roles of alpha 1-AR subtypes could be delineated. (c) 2006 Elsevier Inc. All rights reserved.