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. 1996 Jul 9;93(14):7375–7380. doi: 10.1073/pnas.93.14.7375

Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects.

D K Rohrer 1, K H Desai 1, J R Jasper 1, M E Stevens 1, D P Regula Jr 1, G S Barsh 1, D Bernstein 1, B K Kobilka 1
PMCID: PMC38992  PMID: 8693001

Abstract

At least three distinct beta-adrenergic receptor (beta-AR) subtypes exist in mammals. These receptors modulate a wide variety of processes, from development and behavior, to cardiac function, metabolism, and smooth muscle tone. To understand the roles that individual beta-AR subtypes play in these processes, we have used the technique of gene targeting to create homozygous beta 1-AR null mutants (beta 1-AR -/-) in mice. The majority of beta 1-AR -/- mice die prenatally, and the penetrance of lethality shows strain dependence. Beta l-AR -/- mice that do survive to adulthood appear normal, but lack the chronotropic and inotropic responses seen in wild-type mice when beta-AR agonists such as isoproterenol are administered. Moreover, this lack of responsiveness is accompanied by markedly reduced stimulation of adenylate cyclase in cardiac membranes from beta 1-AR -/- mice. These findings occur despite persistent cardiac beta 2-AR expression, demonstrating the importance of beta 1-ARs for proper mouse development and cardiac function, while highlighting functional differences between beta-AR subtypes.

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