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

DK Rohrer, KH Desai, JR Jasper… - Proceedings of the …, 1996 - National Acad Sciences
DK Rohrer, KH Desai, JR Jasper, ME Stevens, DP Regula Jr, GS Barsh, D Bernstein
Proceedings of the National Academy of Sciences, 1996National Acad Sciences
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 …
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.
National Acad Sciences