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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