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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+4
Generation DefinitionsDonating Investigator Dr. Walter Koch, Duke University Medical Center Appearance
multiple coat colors
Related Genotype: segregating for a, A, Oca2p, Tyrc, and Pde6brd1Description
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
View Strains carrying other alleles of Myh6 (38 strains)
Phenotype
Phenotype Information
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Asthma, Susceptibility to (ADRB2)
Beta-2-Adrenergic Receptor; ADRB2 (ADRB2)
Obesity (ADRB2)
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
- mortality/aging
- premature death
- mean survival time is 307 days compared to over 600 for control mice and most mice die by 1 year of age (MGI Ref ID J:125581)
- behavior/neurological phenotype
- fatigue
- fatigue occurs in mice when approaching 1 year of age (MGI Ref ID J:125581)
- respiratory system phenotype
- respiratory distress
- occurs in mice when approaching 1 year of age (MGI Ref ID J:125581)
- homeostasis/metabolism phenotype
- cyanosis
- occurs in mucosal membranes as mice approach 1 year of age (MGI Ref ID J:125581)
Tg(WTbeta2)4Wjk/0
involves: C57BL/6
- mortality/aging
- premature death
- mice show increased mortality by one year compared to controls (MGI Ref ID J:134706)
- cardiovascular system phenotype
- abnormal cardiac muscle contractility
- cardiac fibrosis
- hearts of 8 month old mice show area of significant fibrosis (MGI Ref ID J:134706)
- homeostasis/metabolism phenotype
- abnormal exercise endurance
- mice have increased exercise tolerance on a treadmill compared to controls at 6 months of age (MGI Ref ID J:134706)
- muscle phenotype
- abnormal cardiac muscle contractility
Tg(WTbeta2)4Wjk/?
Background Not Specified
- cardiovascular system phenotype
- abnormal cardiac muscle relaxation
- left ventricle relaxation is enhanced compared to controls with a mean drop in pressure of 5328 mm Hg versus 3313 mm Hg (MGI Ref ID J:17862)
- increased cardiac muscle contractility
- 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 (MGI Ref ID J:17862)
- these parameters at baseline are equal to those observed in control mice maximally stimulated with isoproterenol (MGI Ref ID J:17862)
- increased ventricle muscle contractility
- the baseline left ventricle dP/dT-max is 70% higher than in controls (MGI Ref ID J:17862)
- administration of isoproterenol fails to increase the dP/dTmax as it does in wild-type controls (MGI Ref ID J:17862)
- this parameter at baseline is equal to those observed in control mice maximally stimulated with isoproterenol (MGI Ref ID J:17862)
- increased heart rate
- muscle phenotype
- abnormal cardiac muscle relaxation
- left ventricle relaxation is enhanced compared to controls with a mean drop in pressure of 5328 mm Hg versus 3313 mm Hg (MGI Ref ID J:17862)
- increased cardiac muscle contractility
- 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 (MGI Ref ID J:17862)
- these parameters at baseline are equal to those observed in control mice maximally stimulated with isoproterenol (MGI Ref ID J:17862)
- increased ventricle muscle contractility
- the baseline left ventricle dP/dT-max is 70% higher than in controls (MGI Ref ID J:17862)
- administration of isoproterenol fails to increase the dP/dTmax as it does in wild-type controls (MGI Ref ID J:17862)
- this parameter at baseline is equal to those observed in control mice maximally stimulated with isoproterenol (MGI Ref ID J:17862)
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 provided by MGI
| Allele Symbol | Tg(WTbeta2)4Wjk | ||
|---|---|---|---|
| Allele Name | transgene insertion 4, Walter Koch | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | TG4; Tg(Myh6-ADRB2)4Wjk; | ||
| Mutation Made By | Dr. Walter Koch, Duke University Medical Center | ||
| Expressed Gene | ADRB2, adrenoceptor beta 2, surface, human | ||
| Promoter | Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, murine, murine | ||
| 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, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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 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 relatedAn 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 516 (Pt 1):19-30. [PubMed: 10066919] [MGI Ref ID J:55224]
Cross HR; Murphy E; Koch WJ; Steenbergen C. 2002. Male and female mice overexpressing the beta(2)-adrenergic receptor exhibit differences in ischemia/reperfusion injury: role of nitric oxide. Cardiovasc Res 53(3):662-71. [PubMed: 11861037] [MGI Ref ID J:162751]
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]
Sheridan DJ; Autelitano DJ; Wang B; Percy E; Woodcock EA; Du XJ. 2000. Beta(2)-adrenergic receptor overexpression driven by alpha-MHC promoter is downregulated in hypertrophied and failing myocardium. Cardiovasc Res 47(1):133-41. [PubMed: 10869539] [MGI Ref ID J:162755]
Thireau J; Aimond F; Poisson D; Zhang B; Bruneval P; Eder V; Richard S; Babuty D. 2010. New insights into sexual dimorphism during progression of heart failure and rhythm disorders. Endocrinology 151(4):1837-45. [PubMed: 20176721] [MGI Ref ID J:168521]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3000.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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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 Information
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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