Do studies in caveolin-knockouts teach us about physiology and pharmacology or instead, the ways mice compensate for 'lost proteins'?
A wide array of phenotypic changes have been reported in mice with knockout of expression of caveolin-1. Neidhold et al. (2007) describe results in this issue that continue this trend by showing that saphenous arteries from adult caveolin-1 knockout mice lack caveolae, lose beta1-adrenoceptor-promoted relaxation, gain beta3-adrenoceptor-promoted relaxation but show no change in vasomotor response to beta2-adrenoceptor activation. Neither the physiological importance for wild-type animals nor the mechanistic basis for these changes is clear. Although the caveolin-1 knockout and wild-type mice express similar levels of the receptor mRNAs, the protein expression of the receptors is not specified and represents, in our view, an important limitation of the study. We also question the physiological relevance of the findings and ask: Do studies in total body/lifespan caveolin-knockout mice further understanding of physiology and pharmacology or do they primarily characterize secondary consequences? We propose that alternative approaches that decrease caveolin expression in a temporally and spatially discrete manner are more likely to facilitate definitive conclusions regarding caveolin-1 and its role in regulation of beta-adrenoceptors and other pharmacological targets.
Insel
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Department of Pharmacology, University of California San Diego, La Jolla, CA 92093-0636, USA. pinsel@ucsd.edu
Patel
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D000222:Adaptation, Physiological; D000818:Animals; D051242:Caveolin 1 / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology*; D023421:Models, Animal; D010600:Pharmacology / Q000379:methods; D010641:Phenotype; D010827:Physiology / Q000379:methods; D015203:Reproducibility of Results
D051242:Caveolin 1