Mice lacking alpha-calcitonin gene-related peptide exhibit normal cardiovascular regulation and neuromuscular development.
alpha-Calcitonin gene-related peptide (alphaCGRP) is a pleiotropic peptide neuromodulator that is widely expressed throughout the Central and peripheral nervous systems. CGRP has been implicated in a variety of physiological processes including peripheral vasodilation, cardiac acceleration nicotinic acetylcholine receptor (AChR) synthesis and function, testicular descent, nociception, carbohydrate metabolism, gastrointestinal motility, neurogenic inflammation, and gastric acid secretion. To provide a better understanding of the physiological role(s) mediated by this peptide neurotransmitter, we have generated alphaCGRP-null mice by targeted modification in embryonic stem cells. Mice lacking alpha CGRP expression demonstrate no obvious phenotypic differences from their wild-type littermates. Detailed analysis of systemic cardiovascular function revealed no differences between control and mutant mice regarding heart rate and blood pressure under basal or exercise-induced conditions and subsequent to pharmacological manipulation. Characterization of neuromuscular junction in morphology including nicotinic receptor localization, terminal sprouting in response to denervation, developmental regulation of AChR subunit expression, and synapse elimination also revealed no differences in alphaCGRP-deficient animals. These results suggest that alphaCGRP is not required for the systemic regulation of cardiovascular hemodynamics or development of the neuromuscular junction.
Lu
J T
JT
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Son
Y J
YJ
Lee
J
J
Jetton
T L
TL
Shiota
M
M
Moscoso
L
L
Niswender
K D
KD
Loewy
A D
AD
Magnuson
M A
MA
Sanes
J R
JR
Emeson
R B
RB
D000375:Aging / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000254:growth & development / Q000294:innervation / Q000502:physiology*; D001483:Base Sequence; D001794:Blood Pressure / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000254:growth & development / Q000294:innervation / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000502:physiology*; D010641:Phenotype; D005082:Physical Exertion; D011978:Receptors, Nicotinic / Q000235:genetics*; D015183:Restriction Mapping; D013234:Stem Cells / Q000502:physiology
D011978:Receptors, Nicotinic; D015740:Calcitonin Gene-Related Peptide