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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N9p (12-FEB-06) Donating Investigator Paul Simpson, VAMC San Francisco and UCSF 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 mo del 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).
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (178 strains)
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Adra1atm1Pcs/Adra1a+
involves: 129X1/SvJ * FVB/N
- cardiovascular system phenotype
- hypotension (MGI Ref ID J:77732)
- heterozygotes are intermediately hypotensive relative to wild-type and homozygous mutant mice
Adra1atm1Pcs/Adra1atm1Pcs
involves: 129X1/SvJ * FVB/N
- cardiovascular system phenotype
- decreased heart rate variability (MGI Ref ID J:77732)
- by ECG telemetry, conscious homozygotes show a 14% reduction in basal heart rate variability, suggesting increased sympathetic balance
- decreased vasoconstriction (MGI Ref ID J:77732)
- homozygotes are chronically hypotensive due to loss of vasoconstriction and consequent reduction of vasomotor tone
- hypotension (MGI Ref ID J:77732)
- 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)
- 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
- no differences in body weight, heart weight, heart histology, blood chemistry, blood cell counts, cardiac output or renal function are observed
This mouse can be used to support research in many areas including:
Cardiovascular Research
Hypotension
Research Tools
lacZ Expression
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Adra1atm1Pcs | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Paul C Simpson | ||
| Allele Type | Targeted (Reporter) | ||
| Mutation Made By | Paul Simpson, VAMC San Francisco and UCSF | ||
| Strain of Origin | 129X1/SvJ | ||
| ES Cell Line Name | RW-4 | ||
| ES Cell Line Strain | 129X1/SvJ | ||
| Site of Expression | lacZ expression is detected in embryonic day 12.5 aged embryos and in adult tissues. | ||
| Gene Symbol and Name | Adra1a, adrenergic receptor, alpha 1a | ||
| Chromosome | 14 | ||
| Gene Common Name(s) | ADRA1C; ADRA1L1; ALPHA1AAR; Adra1c; [a]1a; adrenergic receptor, alpha 1c; | ||
| 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. [MGI Ref ID J:77732] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Adra1atm1Pcs, SEP PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
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):9474-9. [PubMed: 12093905] [MGI Ref ID J:77732]
Additional References
Adra1atm1Pcs relatedHosoda C; Hiroyama M; Sanbe A; Birumachi J; Kitamura T; Cotecchia S; Simpson PC; Tsujimoto G; Tanoue A. 2007. Blockade of both alpha1A- and alpha1B-adrenergic receptor subtype signaling is required to inhibit neointimal formation in the mouse femoral artery. Am J Physiol Heart Circ Physiol 293(1):H514-9. [PubMed: 17384126] [MGI Ref ID J:126035]
Huang Y; Wright CD; Merkwan CL; Baye NL; Liang Q; Simpson PC; O'Connell TD. 2007. An alpha1A-adrenergic-extracellular signal-regulated kinase survival signaling pathway in cardiac myocytes. Circulation 115(6):763-72. [PubMed: 17283256] [MGI Ref ID J:132328]
McCloskey DT; Turnbull L; Swigart P; O'Connell TD; Simpson PC; Baker AJ. 2003. Abnormal myocardial contraction in alpha(1A)- and alpha(1B)-adrenoceptor double-knockout mice. J Mol Cell Cardiol 35(10):1207-16. [PubMed: 14519431] [MGI Ref ID J:102648]
O'Connell TD; Ishizaka S; Nakamura A; Swigart PM; Rodrigo MC; Simpson GL; Cotecchia S; Rokosh DG; Grossman W; Foster E; Simpson PC. 2003. The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse. J Clin Invest 111(11):1783-91. [PubMed: 12782680] [MGI Ref ID J:83876]
O'Connell TD; Swigart PM; Rodrigo MC; Ishizaka S; Joho S; Turnbull L; Tecott LH; Baker AJ; Foster E; Grossman W; Simpson PC. 2006. Alpha1-adrenergic receptors prevent a maladaptive cardiac response to pressure overload. J Clin Invest 116(4):1005-15. [PubMed: 16585965] [MGI Ref ID J:107811]
Turnbull L; McCloskey DT; O'Connell TD; Simpson PC; Baker AJ. 2003. Alpha 1-adrenergic receptor responses in alpha 1AB-AR knockout mouse hearts suggest the presence of alpha 1D-AR. Am J Physiol Heart Circ Physiol 284(4):H1104-9. [PubMed: 12595294] [MGI Ref ID J:83036]
Zhang H; Cotecchia S; Thomas SA; Tanoue A; Tsujimoto G; Faber JE. 2004. Gene deletion of dopamine beta-hydroxylase and alpha1-adrenoceptors demonstrates involvement of catecholamines in vascular remodeling. Am J Physiol Heart Circ Physiol 287(5):H2106-14. [PubMed: 15231500] [MGI Ref ID J:95771]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as heterozygotes or homozygotes.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
The Jackson Laboratory's Genotype Promise
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.Ordering and Purchasing Information
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Contact information
General inquiries
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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