Physiological consequences of β-adrenergic receptor disruption
Activation of β-adrenergic receptors (β-ARs) in vivo is an important means by which animals regulate cardiac performance, vascular tone, lipid and carbohydrate metabolism, and behavior. The advent of targeted gene disruption in mice has led to significant advances in our understanding of the role that β-AR subtypes play in these processes, and this technique has become an important tool for the study of G protein coupled receptors in general. To date, targeted disruption of both β1- and β3-ARs in mice has been reported. Mice lacking β1-ARs are unresponsive to cardiac β-AR stimulation, suggesting that neither β2- nor β3-ARs couple to inotropic or chronotropic responses in the mouse. Conversely, mice lacking β3-ARs retain at least some adipose β-AR responsiveness through remaining β1- and β2-ARs, suggesting that all three β-AR subtypes mediate similar functions in this tissue. While these knockout models have been extremely valuable tools for revealing the roles that individual β-ARs play in whole animal physiology, it is also useful to integrate the results of experiments derived from either transgenic overexpression of β-ARs or purely pharmacological approaches to the study of β-AR function in order to create a comprehensive model of β-AR function in vivo.
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