B6.129X1-Adra1a^tm1Pcs/J

Stock number: 005039
Product name: α1A/C KO
Research areas: Cardiovascular Research, Research Tools

Description

These Adra1a knock-in/knock-out mice exhibit hypotension and express beta-galactosidase in resistance arteries. They are suitable for use in applications related to the study of the cardiovascular system, cardiomyopathy and hypotension.

Detailed description

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.

Development

A targeting vector containing neomycin resistance and beta-galactosidase (lacZ) genes was used to disrupt exon 1 and 415 bp of intron 1. The construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 5 generations (February 2004).

Allele

Symbol: Adra1a^tm1Pcs
Name: targeted mutation 1, Paul C Simpson
MGI accession ID: MGI:2387663
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Adra1a
Marker name: adrenergic receptor, alpha 1a
Chromosome: 14
Strain of origin: 129X1/SvJ
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ expression is detected in embryonic day 12.5 aged embryos and in adult tissues.
Molecular note: Exon 1 and 415 bp of intron 1 were replaced with a cassette containing lacZ and neo genes. The deleted region encoded the receptor and transmembrane regions 1 through 5. The absence of transcript was confirmed by both RT-PCR analysis and RNAse protection. Binding assays showed adrenergic receptor binding to be reduced by approximately 50% in brain and kidney tissues and by 70% in heart tissue, all obtained from homozygous mutant mice. Expression of beta-galactosidase was driven by the endogenous promoter.