Description

Strain Information

Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N?+4   Donating Investigator Walter Koch,   Duke University Medical Center

Appearance
multiple coat colors
Related Genotype: segregating for a, A, Oca2^p, Tyr^c, and Pde6b^rd1

Description
These transgenic mice exhibit increased basal myocardial adenylyl cyclase activity, enhanced atrial contractility, and increased left ventricular function in vivo; these parameters at baseline in the transgenic animals were equal to those observed in control animals maximally stimulated with isoproterenol. Mice carrying this transgene display a marked overexpression of the human beta-2 adrenergic receptor (~200 fold increase).

Development
This strain was developed in the laboratory of Dr. Walter Koch at Duke University Medical Center. The transgene consists of the human beta-2 adrenergic receptor, a SV40 introl/polyA sequence used for screening of mice, and the murine alpha-myosin heavy chain promoter. Transgenic mice were created with cardiac-specific overexpression of the Beta2 adrenergic receptor.

Control Information

	Control
	Noncarrier
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Myh6

002640	B6;SJL-Tg(Myh6-ADRBK1)27Wjk/J
002637	B6SJL-Tg(CAMalpha1b)7Wjk/J
002639	B6SJL-Tg(Myh6-ADRBK1)12Wjk/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

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

Tg(WTbeta2)4Wjk/0

        B6.Cg-Tg(WTbeta2)4Wjk

• life span-post-weaning/aging
• premature death (MGI Ref ID J:125581)
  • mean survival time is 307 days compared to over 600 for control mice and most mice die by 1 year of age
• behavior/neurological phenotype
• fatigue (MGI Ref ID J:125581)
  • fatigue occurs in mice when approaching 1 year of age
• respiratory system phenotype
• respiratory distress (MGI Ref ID J:125581)
  • occurs in mice when approaching 1 year of age
• homeostasis/metabolism phenotype
• cyanosis (MGI Ref ID J:125581)
  • occurs in mucosal membranes as mice approach 1 year of age

Tg(WTbeta2)4Wjk/0

        involves: C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:134706)
  • mice show increased mortality by one year compared to controls
• cardiovascular system phenotype
• abnormal cardiac muscle contractility (MGI Ref ID J:134706)
  • mice have increased fractional shortening at 4 months of age but not 8 months of age
  • by 12 months of age, fractional shortening has become significantly impaired
• cardiac fibrosis (MGI Ref ID J:134706)
  • hearts of 8 month old mice show area of significant fibrosis
• homeostasis/metabolism phenotype
• abnormal exercise endurance (MGI Ref ID J:134706)
  • mice have increased exercise tolerance on a treadmill compared to controls at 6 months of age
• muscle phenotype
• abnormal cardiac muscle contractility (MGI Ref ID J:134706)
  • mice have increased fractional shortening at 4 months of age but not 8 months of age
  • by 12 months of age, fractional shortening has become significantly impaired

Tg(WTbeta2)4Wjk/?

        Background Not Specified

• cardiovascular system phenotype
• abnormal cardiac muscle relaxation (MGI Ref ID J:17862)
  • left ventricle relaxation is enhanced compared to controls with a mean drop in pressure of 5328 mm Hg versus 3313 mm Hg
• increased cardiac muscle contractility (MGI Ref ID J:17862)
  • the isometric tension of isolated left atria is three times that of controls while the isometric tension of the right atria is about 75% higher than in wild-type controls
  • these parameters at baseline are equal to those observed in control mice maximally stimulated with isoproterenol
• increased ventricle muscle contractility (MGI Ref ID J:17862)
  • the baseline left ventricle dP/dT-max is 70% higher than in controls
  • administration of isoproterenol fails to increase the dP/dTmax as it does in wild-type controls
  • this parameter at baseline is equal to those observed in control mice maximally stimulated with isoproterenol
• increased heart rate (MGI Ref ID J:17862)
  • the mean heart rate is about 425 bpm compared to 340 bpm in control mice
  • there is about a 50% increase in the heart rate of isolated right atria
• muscle phenotype
• abnormal cardiac muscle relaxation (MGI Ref ID J:17862)
  • left ventricle relaxation is enhanced compared to controls with a mean drop in pressure of 5328 mm Hg versus 3313 mm Hg
• increased cardiac muscle contractility (MGI Ref ID J:17862)
  • the isometric tension of isolated left atria is three times that of controls while the isometric tension of the right atria is about 75% higher than in wild-type controls
  • these parameters at baseline are equal to those observed in control mice maximally stimulated with isoproterenol
• increased ventricle muscle contractility (MGI Ref ID J:17862)
  • the baseline left ventricle dP/dT-max is 70% higher than in controls
  • administration of isoproterenol fails to increase the dP/dTmax as it does in wild-type controls
  • this parameter at baseline is equal to those observed in control mice maximally stimulated with isoproterenol

View Research Applications

Research Applications

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

ADRB2 related

Cardiovascular Research
Heart Abnormalities

Internal/Organ Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(WTbeta2)4Wjk
Allele Name		transgene insertion 4, Walter Koch
Allele Type		Transgenic (random, expressed)
Common Name(s)		TG4;
Mutation Made By		Walter Koch,   Duke University Medical Center
Expressed Gene		ADRB2, adrenergic, beta-2-, receptor, surface, human
Promoter		Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, mouse, laboratory
Molecular Note		The transgene consists of the human beta-2 adrenergic receptor (ADRB2), an SV40 intron/polyA sequence, and the murine myosin, heavy polypeptide 6, cardiac muscle, alpha (Myh6) promoter which directs cardiac-specific overexpression of ADRB2. Transgene expression is detected in cardiac myocytes at levels 200 times greater than in human cardiac tissue. [MGI Ref ID J:17862]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(WTbeta2)4Wjk, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Milano CA; Allen LF; Rockman HA; Dolber PC; McMinn TR; Chien KR; Johnson TD; Bond RA; Lefkowitz RJ. 1994. Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor [see comments] Science 264(5158):582-6. [PubMed: 8160017]  [MGI Ref ID J:17862]

Additional References

An RH; Heath BM; Higgins JP; Koch WJ; Lefkowitz RJ; Kass RS. 1999. beta(2)-adrenergic receptor overexpression in the developing mouse heart: evidence for targeted modulation of ion channels. J Physiol (Lond) 516 (Pt 1):19-30. [PubMed: 10066919]  [MGI Ref ID J:55224]

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]

Tg(WTbeta2)4Wjk related

An RH; Heath BM; Higgins JP; Koch WJ; Lefkowitz RJ; Kass RS. 1999. beta(2)-adrenergic receptor overexpression in the developing mouse heart: evidence for targeted modulation of ion channels. J Physiol (Lond) 516 (Pt 1):19-30. [PubMed: 10066919]  [MGI Ref ID J:55224]

Dilly KW; Kurokawa J; Terrenoire C; Reiken S; Lederer WJ; Marks AR; Kass RS. 2004. Overexpression of beta2-adrenergic receptors cAMP-dependent protein kinase phosphorylates and modulates slow delayed rectifier potassium channels expressed in murine heart: evidence for receptor/channel co-localization. J Biol Chem 279(39):40778-87. [PubMed: 15272004]  [MGI Ref ID J:93340]

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]

Du XJ; Autelitano DJ; Dilley RJ; Wang B; Dart AM; Woodcock EA. 2000. beta(2)-adrenergic receptor overexpression exacerbates development of heart failure after aortic stenosis. Circulation 101(1):71-7. [PubMed: 10618307]  [MGI Ref ID J:60080]

Du XJ; Gao XM; Wang B; Jennings GL; Woodcock EA; Dart AM. 2000. Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing beta(2)-adrenergic receptors in the heart. Cardiovasc Res 48(3):448-54. [PubMed: 11090840]  [MGI Ref ID J:128583]

Foerster K; Groner F; Matthes J; Koch WJ; Birnbaumer L; Herzig S. 2003. Cardioprotection specific for the G protein Gi2 in chronic adrenergic signaling through beta 2-adrenoceptors. Proc Natl Acad Sci U S A 100(24):14475-80. [PubMed: 14612574]  [MGI Ref ID J:125581]

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]

Gaussin V; Tomlinson JE; Depre C; Engelhardt S; Antos CL; Takagi G; Hein L; Topper JN; Liggett SB; Olson EN; Lohse MJ; Vatner SF; Vatner DE. 2003. Common genomic response in different mouse models of beta-adrenergic-induced cardiomyopathy. Circulation 108(23):2926-33. [PubMed: 14623810]  [MGI Ref ID J:102945]

Grandy SA; Denovan-Wright EM; Ferrier GR; Howlett SE. 2004. Overexpression of human beta2-adrenergic receptors increases gain of excitation-contraction coupling in mouse ventricular myocytes. Am J Physiol Heart Circ Physiol 287(3):H1029-38. [PubMed: 15155261]  [MGI Ref ID J:95592]

Hasseldine AR; Harper EA; Black JW. 2003. Cardiac-specific overexpression of human beta2 adrenoceptors in mice exposes coupling to both Gs and Gi proteins. Br J Pharmacol 138(7):1358-66. [PubMed: 12711637]  [MGI Ref ID J:133731]

Heubach JF; Trebess I; Wettwer E; Himmel HM; Michel MC; Kaumann AJ; Koch WJ; Harding SE; Ravens U. 1999. L-type calcium current and contractility in ventricular myocytes from mice overexpressing the cardiac beta 2-adrenoceptor. Cardiovasc Res 42(1):173-82. [PubMed: 10435008]  [MGI Ref ID J:130595]

Peter PS; Brady JE; Yan L; Chen W; Engelhardt S; Wang Y; Sadoshima J; Vatner SF; Vatner DE. 2007. Inhibition of p38 alpha MAPK rescues cardiomyopathy induced by overexpressed beta 2-adrenergic receptor, but not beta 1-adrenergic receptor. J Clin Invest 117(5):1335-43. [PubMed: 17446930]  [MGI Ref ID J:122039]

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

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
	Noncarrier
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.

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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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.

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