Clinical implications from studies of alpha1 adrenergic receptor knockout mice

alpha1-Adrenergic receptors (alpha1-ARs) modulate a large number of physiological functions in cardiovascular and noncardiovascular tissues. Because individual members of the alpha1-AR family (alpha1A-, alpha1B-, and alpha1D-ARs) have overlapping expression profiles in most tissues, elucidation of the precise physiological roles of individual alpha1-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 alpha1-AR genes. Recent studies on these mutant mouse strains are discussed in this article, with an emphasis on the role of alpha1-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 alpha1-ARs. By combining gene targeting techniques with pharmacological tools, the specific roles of alpha1-AR subtypes could be delineated.