Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by RT-PCR or RNase protection assay analysis. Total alpha-1 adrenergic receptor binding is reduced by 50% in brain and kidney, and by approximately 30% in heart. Expression of the beta-galactosidase reporter gene under the control of the endogenous gene promoter, is detected in embryonic day 12.5 aged embryos and in adult tissues closely mimicking the endogenous gene expression pattern. The resistance arteries, abdominal aorta, celiac, renal, mesenteric, hepatic, splenic, gastric, testicular, ovarian, iliac, femoral and tail arteries, as well as dermal arterioles, are positive for beta-galactosidase staining. Homozygotes are hypotensive with an 8-12% reduction from wildtype control blood pressure levels, as measured in conscious animals at rest. Administration of an alpha-1 adrenergic receptor specific agonist has no effect on mean arterial pressure in homozygotes. The baroreflex, blood pressure-heart rate relation, is altered indicating chronic hypotension. Heterozygotes exhibit an intermediary phenotype of beta-galactosidase expression and mean arterial blood pressure at rest, but the alpha-1 adrenergic receptor specific agonist causes hypertension. This mutant mouse strain represents a model that may be useful in studies of clinical hypertension and blood pressure regulation.
