Description

Strain Information

Former Names B6;SJL-Tg(minBARKct)27Wjk/J    (Changed: 04-MAY-07 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F8p   Donating Investigator Walter Koch,   Duke University Medical Center

Description
Mice carrying this transgene overexpress a truncated form of the bovine beta-adrenergic receptor kinase-1 containing only the last 194 amino acids of the ADRBK1 protein. The truncated protein inhibits endogenous beta-adrenergic receptor kinase-1 by blocking beta-adrenergic receptor desensitization. This myocardial inhibition increases cardiac function of homozygotes under basal conditions and leads to supersensitization to beta-agonists. This strain may serve as a model for increased left ventricular performance, a novel method of positive intropy, and enhanced beta-adrenergic signalling.

Control Information

	Control
	100012 B6SJLF1/J	(approximate)
	000664 C57BL/6J	(approximate)
	000686 SJL/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Myh6

002637	B6SJL-Tg(CAMalpha1b)7Wjk/J
002639	B6SJL-Tg(Myh6-ADRBK1)12Wjk/J
002638	B6SJL-Tg(WTbeta2)4Wjk/J
006768	D2.Cg-Tg(Myh6-Zfpm2)1Sho/EiJ
002535	FVB/N-Tg(ANX6)2Agh/J

View Strains carrying other alleles of Myh6     (5 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(Myh6-ADRBK1)27Wjk/0

        involves: C57BL/6 * SJL

• cardiovascular system phenotype
• increased cardiac muscle contractility (MGI Ref ID J:134706)
  • mice have increased fractional shortening from 4 to at least 12 months of age
• increased left ventricle diastolic pressure (MGI Ref ID J:37034)
  • both the left ventricular dP/dTmin and dP/dTmax are significantly increased at baseline
  • increases in pressure are enhanced with administration of the beta-agonist isoproterenol
  • both the left ventricular dP/dTmin and dP/dTmax are significantly increased about 25% at baseline
  • increases in pressure are enhanced with administration of the beta-agonist isoproterenol
• increased left ventricle systolic pressure (MGI Ref ID J:37034)
  • left ventricular systolic pressure is increased at baseline
  • increases in pressure are enhanced with administration of the beta-agonist isoproterenol
• muscle phenotype
• increased cardiac muscle contractility (MGI Ref ID J:134706)
  • mice have increased fractional shortening from 4 to at least 12 months of age

View Research Applications

Research Applications

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

Cardiovascular Research
Heart Abnormalities

Internal/Organ Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(Myh6-ADRBK1)27Wjk
Allele Name		transgene insertion 27, Walter Koch
Allele Type		Transgenic (random, expressed)
Common Name(s)		BetaARKct; TG betaARKct; TGMini27; Tg(minBARKct)27Wjk;
Mutation Made By		Walter Koch,   Duke University Medical Center
Strain of Origin		(C57BL/6 x SJL)F1
Expressed Gene		ADRBK1, adrenergic, beta, receptor kinase 1, human
Promoter		Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, mouse, laboratory
Molecular Note		Sequence encoding the carboxyl terminus of the bovine adrenergic receptor kinase, beta 1 (ADRBK1) (residues 495 through 689) was ligated to a 5.5 kb fragment of the murine adult myosin, heavy polypeptide 6, cardiac muscle, alpha (Myh6) promoter. The resultant 194 residue carboxyl terminal peptide was detected by Western blot analysis and inhibits endogenous beta-adrenergic receptor kinase-1 by blocking beta-adrenergic receptor desensitization. The Myh6 promoter drives expression in myocardial tissue. [MGI Ref ID J:37034]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Myh6-ADRBK1)27Wjk, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Koch WJ; Rockman HA; Samama P; Hamilton RA; Bond RA; Milano CA; Lefkowitz RJ. 1995. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science 268(5215):1350-3. [PubMed: 7761854]  [MGI Ref ID J:37034]

Additional References

Tg(Myh6-ADRBK1)27Wjk related

Akhter SA; Eckhart AD; Rockman HA; Shotwell K; Lefkowitz RJ; Koch WJ. 1999. In vivo inhibition of elevated myocardial beta-adrenergic receptor kinase activity in hybrid transgenic mice restores normal beta-adrenergic signaling and function. Circulation 100(6):648-53. [PubMed: 10441103]  [MGI Ref ID J:127858]

Dorn GW 2nd; Tepe NM; Lorenz JN; Koch WJ; Liggett SB. 1999. Low- and high-level transgenic expression of beta2-adrenergic receptors differentially affect cardiac hypertrophy and function in Galphaq- overexpressing mice. Proc Natl Acad Sci U S A 96(11):6400-5. [PubMed: 10339599]  [MGI Ref ID J:55199]

Eckhart AD; Fentzke RC; Lepore J; Lang R; Lin H; Lefkowitz RJ; Koch WJ; Leiden JM. 2002. Inhibition of betaARK1 restores impaired biochemical beta-adrenergic receptor responsiveness but does not rescue CREB(A133) induced cardiomyopathy. J Mol Cell Cardiol 34(6):669-77. [PubMed: 12054854]  [MGI Ref ID J:127503]

Esposito G; Prasad SV; Rapacciuolo A; Mao L; Koch WJ; Rockman HA. 2001. Cardiac overexpression of a G(q) inhibitor blocks induction of extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase activity in in vivo pressure overload. Circulation 103(10):1453-8. [PubMed: 11245652]  [MGI Ref ID J:135011]

Freeman K; Lerman I; Kranias EG; Bohlmeyer T; Bristow MR; Lefkowitz RJ; Iaccarino G; Koch WJ; Leinwand LA. 2001. Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J Clin Invest 107(8):967-74. [PubMed: 11306600]  [MGI Ref ID J:134706]

Rockman HA; Chien KR; Choi DJ; Iaccarino G; Hunter JJ; Ross J Jr; Lefkowitz RJ; Koch WJ. 1998. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc Natl Acad Sci U S A 95(12):7000-5. [PubMed: 9618528]  [MGI Ref ID J:48062]

Rockman HA; Choi DJ; Akhter SA; Jaber M; Giros B; Lefkowitz RJ; Caron MG; Koch WJ. 1998. Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem 273(29):18180-4. [PubMed: 9660778]  [MGI Ref ID J:48681]

Tachibana H; Naga Prasad SV; Lefkowitz RJ; Koch WJ; Rockman HA. 2005. Level of beta-adrenergic receptor kinase 1 inhibition determines degree of cardiac dysfunction after chronic pressure overload-induced heart failure. Circulation 111(5):591-7. [PubMed: 15668342]  [MGI Ref ID J:108555]

Tong H; Rockman HA; Koch WJ; Steenbergen C; Murphy E. 2004. G protein-coupled receptor internalization signaling is required for cardioprotection in ischemic preconditioning. Circ Res 94(8):1133-41. [PubMed: 15031261]  [MGI Ref ID J:98928]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

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

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.

Control Information

	Control
	100012 B6SJLF1/J	(approximate)
	000664 C57BL/6J	(approximate)
	000686 SJL/J	(approximate)
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

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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.

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Terms of Use

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General Terms and Conditions

Contact information

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fax:	207-288-6655

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