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Gene Substitution/Knockout to Delineate the Role of α 2 ‐Adrenoceptor Subtypes in Mediating Central Effects of Catecholamines and Imidazolines
Author(s) -
HEIN L.,
LIMBIRD L. E.,
EGLEN R. M.,
KOBILKA B. K.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb09368.x
Subject(s) - receptor , gene knockout , adrenergic receptor , agonist , endocrinology , biology , sympathetic nervous system , imidazoline receptor , gene targeting , medicine , transgene , stimulation , knockout mouse , central nervous system , microbiology and biotechnology , gene , genetics , blood pressure
Adrenergic receptors form the interface between the sympathetic nervous system and the cardiovascular system as well as many endocrine and parenchymal tissues. For the three α 2 ‐adrenergic receptors (α 2A , α 2B , and α 2C ), genetic mouse models have been developed that can be used to elucidate the physiologic function of each receptor subtype in vivo . Different strategies for homologous recombination in embryonic stem cells were applied to generate lines of mice with gene knockouts of the individual α 2 ‐receptor subtypes (α 2A ‐KO, α 2B ‐KO, and α 2C ‐KO) or with a substitution of a mutant receptor at the wild‐type locus (α 2 ‐D79N). In these transgenic mice, the cardiovascular effects of α 2 ‐agonists and imidazoline;i 1 receptor agonists were tested. Stimulation of α 2B receptors in vascular smooth muscle produces hypertension and counteracts the clinically beneficial hypotensive effect of stimulating α 2A receptors in the central nervous system.