Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Susanna Cotecchia,   Institut de Pharmacologie et de Toxicolo

Description
Mice that are homozygous null for the targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Adra1b transcripts are detected. The amount of alpha 1 adrenergic recptor binding activity as measured by radioligand assays is dramatically decreased in homozygous liver, heart and cerebral cortex. The blood pressure response induced by increasing doses of phenylephrine is reduced by 45% in comparison to wild type mice. Similarly, phenylephrine-induced contraction of aortic tissue is diminished 25%. This mutant mouse strain represents a model that may be useful in studies related to blood pressure regulation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 1. The construct was electroporated into 129P2/OlaHsd-derived HM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.

Related Strains

Strains carrying other alleles of Adra1b

002637

B6SJL-Tg(CAMalpha1b)7Wjk/J

View Strains carrying other alleles of Adra1b     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Adra1b^tm1Cta/Adra1b^tm1Cta

        involves: 129P2/OlaHsd

• cardiovascular system phenotype
• abnormal blood pressure (MGI Ref ID J:43591)
  • mean arterial blood pressure response to phenylephrine is decreased by 45%
  • mean arterial blood pressure response to norepinephrine is also decreased although to a lesser extent than seen with phenylephrine
• decreased blood pressure (MGI Ref ID J:103581)
  • exhibit impaired pressor response to a hypotensive stimulus, with marked attenuation in the change in systolic blood pressure and in the percent change in the end-systolic pressure-volume relationship after transient bilateral carotid occlusion
• decreased systolic blood pressure (MGI Ref ID J:103581)
  • baseline systolic blood pressure and Ea are lower
• abnormal left ventricle morphology (MGI Ref ID J:103581)
  • left ventricular volume is higher
• decreased cardiac muscle contractility (MGI Ref ID J:43591)
  • phenylephrine-induced contractions of aortic rings are decreased by 25%
  • baseline myocardial contractility is lower, as reflected by dP/dt
  • transient bilateral carotid occlusion results in a minimal increase in myocardial contractility instead of the enhanced contractility seen in wild-type
• decreased heart rate (MGI Ref ID J:103581)
  • transient bilateral carotid occlusion results in a decrease in heart rate compared to a slight increase in treated wild-type, however baseline heart rate is normal
• decreased vasoconstriction (MGI Ref ID J:103581)
  • exhibit a reduction in mesenteric vascular responses to endogenous norepinephrine compared to wild-type, indicating reduced vasoconstriction in response to norepinephrine
• muscle phenotype
• decreased cardiac muscle contractility (MGI Ref ID J:43591)
  • phenylephrine-induced contractions of aortic rings are decreased by 25%
  • baseline myocardial contractility is lower, as reflected by dP/dt
  • transient bilateral carotid occlusion results in a minimal increase in myocardial contractility instead of the enhanced contractility seen in wild-type
• decreased vascular smooth muscle contraction (MGI Ref ID J:103581)
  • mesenteric microvascular contractile responses to endogenous norepinephrine are depressed compared to wild-type
• behavior/neurological phenotype
• decreased exploration in new environment (MGI Ref ID J:102553)
  • 4-5 month old homozygotes show significantly reduced horizontal exploratory activity and a reduced rearing behavior (vertical activity) in the open field
• impaired passive avoidance behavior (MGI Ref ID J:102553)
  • 4-5 month old homozygotes show impaired retention of an inhibitory avoidance task after receiving a stressful electric stimuli
• nervous system phenotype
• abnormal baroreceptor physiology (MGI Ref ID J:103581)
  • transient bilateral carotid occlusion to test cardiovascular responses to a hypotensive stimuli produced an attenuated pressor response, indicating an abnormal baroreflex activity

View Research Applications

Research Applications

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

Adra1b^tm1Cta related

Cardiovascular Research
Heart Abnormalities
Hypotension
Vascular Defects

Internal/Organ Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information

Allele Symbol		Adra1btm1Cta
Allele Name		targeted mutation 1, Susanna Cotecchia
Allele Type		Targeted (knock-out)
Common Name(s)		alpha1b-; alpha1b-AR-;
Mutation Made By		Susanna Cotecchia,   Institut de Pharmacologie et de Toxicolo
Strain of Origin		129P2/OlaHsd-Hprt1
ES Cell Line Name		HM-1
ES Cell Line Strain		129P2/OlaHsd-Hprt1
Gene Symbol and Name		Adra1b, adrenergic receptor, alpha 1b
Chromosome		11
Gene Common Name(s)		ADRA1; ALPHA1BAR; [a]1b; alpha1B-adrenergic receptor;
Molecular Note		A genomic fragment containing exon 1 was deleted and replaced with a neomycin selection cassette. RT-PCR analysis confirmed that no transcript is produced from this allele. [MGI Ref ID J:43591]

Genotyping

Genotyping Information

Genotyping Protocols

Adra1b^tm1Cta, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Adra1b^tm1Cta related

Auclair A; Cotecchia S; Glowinski J; Tassin JP. 2002. D-amphetamine fails to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: relationship between functional and nonfunctional dopamine release. J Neurosci 22(21):9150-4. [PubMed: 12417637]  [MGI Ref ID J:123996]

Battaglia G; Fornai F; Busceti CL; Lembo G; Nicoletti F; De Blasi A. 2003. Alpha-1B adrenergic receptor knockout mice are protected against methamphetamine toxicity. J Neurochem 86(2):413-21. [PubMed: 12871582]  [MGI Ref ID J:84429]

Burcelin R; Uldry M; Foretz M; Perrin C; Dacosta A; Nenniger-Tosato M; Seydoux J; Cotecchia S; Thorens B. 2004. Impaired glucose homeostasis in mice lacking the alpha1b-adrenergic receptor subtype. J Biol Chem 279(2):1108-15. [PubMed: 14581480]  [MGI Ref ID J:87718]

Cavalli A; Lattion AL; Hummler E; Nenniger M; Pedrazzini T; Aubert JF; Michel MC; Yang M; Lembo G; Vecchione C; Mostardini M; Schmidt A; Beermann F; Cotecchia S. 1997. Decreased blood pressure response in mice deficient of the alpha1b-adrenergic receptor. Proc Natl Acad Sci U S A 94(21):11589-94. [PubMed: 9326654]  [MGI Ref ID J:43591]

Drouin C; Darracq L; Trovero F; Blanc G; Glowinski J; Cotecchia S; Tassin JP. 2002. Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates. J Neurosci 22(7):2873-84. [PubMed: 11923452]  [MGI Ref ID J:76004]

Faber JE; Szymeczek CL; Cotecchia S; Thomas SA; Tanoue A; Tsujimoto G; Zhang H. 2007. Alpha1-adrenoceptor-dependent vascular hypertrophy and remodeling in murine hypoxic pulmonary hypertension. Am J Physiol Heart Circ Physiol 292(5):H2316-23. [PubMed: 17220188]  [MGI Ref ID J:125945]

Hosoda 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]

Hosoda C; Koshimizu TA; Tanoue A; Nasa Y; Oikawa R; Tomabechi T; Fukuda S; Shinoura H; Oshikawa S; Takeo S; Kitamura T; Cotecchia S; Tsujimoto G. 2005. Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation. Mol Pharmacol 67(3):912-22. [PubMed: 15598970]  [MGI Ref ID J:110125]

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]

Knauber J; Muller WE. 2000. Decreased exploratory activity and impaired passive avoidance behaviour in mice deficient for the alpha(1b)-adrenoceptor. Eur Neuropsychopharmacol 10(6):423-7. [PubMed: 11115730]  [MGI Ref ID J:102553]

Koshimizu T; Tanoue A; Tsujimimoto G. 2007. Clinical implications from studies of alpha1 adrenergic receptor knockout mice Biochem Pharmacol 73(8):1107-12. [PubMed: 17141736]  [MGI Ref ID J:117338]

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]

Mhaouty-Kodja S; Lozach A; Habert R; Tanneux M; Guigon C; Brailly-Tabard S; Maltier JP; Legrand-Maltier C. 2007. Fertility and spermatogenesis are altered in {alpha}1b-adrenergic receptor knockout male mice. J Endocrinol 195(2):281-92. [PubMed: 17951539]  [MGI Ref ID J:125763]

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]

Salomon L; Lanteri C; Glowinski J; Tassin JP. 2006. Behavioral sensitization to amphetamine results from an uncoupling between noradrenergic and serotonergic neurons. Proc Natl Acad Sci U S A 103(19):7476-81. [PubMed: 16648258]  [MGI Ref ID J:109449]

Spreng M; Cotecchia S; Schenk F. 2001. A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities. Neurobiol Learn Mem 75(2):214-29. [PubMed: 11222061]  [MGI Ref ID J:68177]

Szondy Z; Mastroberardino PG; Varadi J; Farrace MG; Nagy N; Bak I; Viti I; Wieckowski MR; Melino G; Rizzuto R; Tosaki A; Fesus L; Piacentini M. 2006. Tissue transglutaminase (TG2) protects cardiomyocytes against ischemia/reperfusion injury by regulating ATP synthesis. Cell Death Differ 13(10):1827-9. [PubMed: 16528383]  [MGI Ref ID J:126414]

Townsend SA; Jung AS; Hoe YS; Lefkowitz RY; Khan SA; Lemmon CA; Harrison RW; Lee K; Barouch LA; Cotecchia S; Shoukas AA; Nyhan D; Hare JM; Berkowitz DE. 2004. Critical role for the alpha-1B adrenergic receptor at the sympathetic neuroeffector junction. Hypertension 44(5):776-82. [PubMed: 15466664]  [MGI Ref ID J:103581]

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]

Vecchione C; Fratta L; Rizzoni D; Notte A; Poulet R; Porteri E; Frati G; Guelfi D; Trimarco V; Mulvany MJ; Agabiti-Rosei E; Trimarco B; Cotecchia S; Lembo G. 2002. Cardiovascular influences of alpha1b-adrenergic receptor defect in mice. Circulation 105(14):1700-7. [PubMed: 11940550]  [MGI Ref ID J:128670]

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	This strain originated on a B6;129P2 background and has been backcrossed to C57BL/6 for at least seven generations.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

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.

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Tel: 800.422.6423 or 207.288.5845
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Terms of Use

Terms of Use

General Terms and Conditions

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.