• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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

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.

Pubmed ID: 8693001


  • Rohrer DK
  • Desai KH
  • Jasper JR
  • Stevens ME
  • Regula DP
  • Barsh GS
  • Bernstein D
  • Kobilka BK


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

July 9, 1996

Associated Grants


Mesh Terms

  • Adenylate Cyclase
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Aging
  • Animals
  • Cell Membrane
  • Chimera
  • Crosses, Genetic
  • Death
  • Female
  • Gene Expression
  • Heart
  • Heart Rate
  • Heart Ventricles
  • Homozygote
  • Imidazoles
  • Isoproterenol
  • Kinetics
  • Lung
  • Male
  • Methoxyhydroxyphenylglycol
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Myocardial Contraction
  • Myocardium
  • Norepinephrine
  • Receptors, Adrenergic, beta-1
  • Restriction Mapping
  • Stem Cells