Overview

Also Known As:α1A/C KO

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.

Donating Investigator

Paul C. Simpson, VAMC San Francisco and UCSF

Genetic overview

Genetic Background	Generation

Adra1a^tm1Pcs

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Adra1a	adrenergic receptor, alpha 1a

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Research Applications

Cardiovascular Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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).

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	lacZ expression is detected in embryonic day 12.5 aged embryos and in adult tissues.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Rokosh DG; Simpson PC. 2002. Knockout of the alpha 1A/C-adrenergic receptor subtype: the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. Proc Natl Acad Sci U S A 99(14):9474-9PubMed: 12093905 MGI: J:77732

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Genetics

Adra1a^tm1Pcs

Allele Symbol: Adra1a^tm1Pcs

Allele Name	targeted mutation 1, Paul C Simpson
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Adra1a, adrenergic receptor, alpha 1a
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	lacZ expression is detected in embryonic day 12.5 aged embryos and in adult tissues.
Strain of Origin	129X1/SvJ
Chromosome	14
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.
Mutations Made By	Paul Simpson, VAMC San Francisco and UCSF

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cardiovascular Research
- Hypotension
Research Tools
- lacZ Expression

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Adra1a^tm1Pcs/Adra1a^tm1Pcs
involves: 129X1/SvJ * FVB/N

cardiovascular system phenotype

decreased heart rate variability
- by ECG telemetry, conscious homozygotes show a 14% reduction in basal heart rate variability, suggesting increased sympathetic balance

decreased vasoconstriction
- homozygotes are chronically hypotensive due to loss of vasoconstriction and consequent reduction of vasomotor tone

hypotension
- by tail cuff manometer and arterial catheter, conscious homozygotes are hypotensive at rest, with a ~10-15 mm Hg reduction in blood pressure (8-12% of wild-type mice)
- no differences in body weight, heart weight, heart histology, blood chemistry, blood cell counts, cardiac output or renal function are observed
- tail cuff pressure is also reduced in a smaller cohort of homozygotes in the C57BL/6 background whereas heart rate is slightly but not significantly higher relative to wild-type mice

muscle phenotype

decreased vasoconstriction
- homozygotes are chronically hypotensive due to loss of vasoconstriction and consequent reduction of vasomotor tone

Genotype: Adra1a^tm1Pcs/Adra1a⁺
involves: 129X1/SvJ * FVB/N

cardiovascular system phenotype

hypotension
- heterozygotes are intermediately hypotensive relative to wild-type and homozygous mutant mice

References

Rokosh DG; Simpson PC. 2002. Knockout of the alpha 1A/C-adrenergic receptor subtype: the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. Proc Natl Acad Sci U S A 99(14):9474-9PubMed: 12093905 MGI: J:77732

Additional - Adra1a^tm1Pcs related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Adra1a Alternate 2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as heterozygotes or homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the α1A/C KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005039 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Adra1a<tm1Pcs>

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As:α1A/C KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Adra1atm1Pcs

Allele Symbol: Adra1atm1Pcs

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Adra1atm1Pcs/Adra1atm1Pcsinvolves: 129X1/SvJ * FVB/N

cardiovascular system phenotype

muscle phenotype

Genotype: Adra1atm1Pcs/Adra1a+involves: 129X1/SvJ * FVB/N

cardiovascular system phenotype

References

Additional - Adra1atm1Pcs related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Adra1a^tm1Pcs

Allele Symbol: Adra1a^tm1Pcs

Genotype: Adra1a^tm1Pcs/Adra1a^tm1Pcs
involves: 129X1/SvJ * FVB/N

Genotype: Adra1a^tm1Pcs/Adra1a⁺
involves: 129X1/SvJ * FVB/N

Additional - Adra1a^tm1Pcs related