Description

Strain Information

Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N8+N1p   Donating Investigator John Cooke,   Stanford University Medical Center

Description
Hemizygous mice are viable and fertile with no anatomic abnormalities. Transgene expression is observed in aorta, heart, and brain. Transgenic dimethylarginine dimethylaminohydrolase (DDAH) activity is reflected in a reduction of plasma asymmetric dimethylarginine (ADMA). Nitric oxide synthase (NOS) activity is significantly increased in transgenic skeletal and cardiac muscle. Transgenic mice have lower blood pressure and higher heart rate. Transgenic mice may be useful in studies of atherosclerosis, hypertension, hyperlipidemia, hypercholesterolemia, hyperhomocystinemia, diabetes mellitus, stroke, renal failure, preeclampsia, and other conditions associated with vascular pathophysiology and/or cardiovascular disease.

Development
A human DDAH-I cDNA and SV40 derived from a modified human agouti expression vector were placed under control of the human B-actin promoter. This construct was injected into fertilized C57BL/6J eggs. Embryos were transferred into the oviducts of pseudopregnant B6CBAF1 foster mothers. Transgenic males were bred to C57BL/6J approximately 8-10 generations before arrival at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of ACTB

005703	B6.Cg-Tg(ACTFLPe)9205Dym/J
006055	B6.Cg-Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J
003800	B6;SJL-Tg(ACTFLPe)9205Dym/J
005145	C57BL/6-Tg(CAG-OVA)916Jen/J
002981	DBA/2-Tg(xstpx-lacZ)36And/J
003376	FVB/N-Tg(ACTB-cre)2Mrt/J
008200	FVB/N-Tg(CAG-EGFP,-ALPP)2.6Ggc/J
005438	STOCK Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J

View Strains carrying other alleles of ACTB     (8 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(ACTB-DDAH1)1Jpck/0

        involves: C57BL/6J

• cardiovascular system phenotype
• abnormal cardiovascular system physiology (MGI Ref ID J:104238)
• abnormal cardiac stroke volume (MGI Ref ID J:104238)
  • stroke volume is reduced by ~10% in transgenic mice
• decreased blood pressure (MGI Ref ID J:104238)
  • mean arterial pressure is reduced by ~10% compared to controls
• decreased systolic blood pressure (MGI Ref ID J:104238)
  • pressure is lower (105.9 mm Hg) than in age- and weight-matched conscious controls (112.7 mm Hg)
  • systolic pressure difference is greater (13 mm Hg) in anesthetized transgenics (76 mm Hg) compared to controls (89 mm Hg)
• decreased systemic vascular resistance (MGI Ref ID J:104238)
  • systemic vascular resistance is reduced by ~10% compared to controls
• increased heart rate (MGI Ref ID J:104238)
  • transgenic mice display ~10% increase in heart rate
• homeostasis/metabolism phenotype
• abnormal enzyme/ coenzyme level (MGI Ref ID J:104238)
  • nitric oxide synthase (NOS) activity is significantly increased in transgenic skeletal muscle; cardiac tissue homogenates have higher NOS activity
• abnormal nitric oxide homeostasis (MGI Ref ID J:104238)
  • transgenic skeletal muscle homogenates have greater NOS activity

View Research Applications

Research Applications

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

Cardiovascular Research
Heart Abnormalities (tachycardia)
Hypercholesterolemia
Hypertension
Hypotension

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Internal/Organ Research
Heart Abnormalities

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(ACTB-DDAH1)1Jpck
Allele Name		transgene insertion 1, John P Cooke
Allele Type		Transgenic (random, expressed)
Common Name(s)		DDAH;
Mutation Made By		John Cooke,   Stanford University Medical Center
Strain of Origin		C57BL/6J
Expressed Gene		DDAH1, dimethylarginine dimethylaminohydrolase 1, human
Promoter		ACTB, actin, beta, human
Molecular Note		A human DDAH-I cDNA and SV40 derived from a modified human agouti expression vector were placed under control of the human B-actin promoter. [MGI Ref ID J:104238]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(ACTB-DDAH1)1Jpck, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Dayoub H; Achan V; Adimoolam S; Jacobi J; Stuehlinger MC; Wang BY; Tsao PS; Kimoto M; Vallance P; Patterson AJ; Cooke JP. 2003. Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis: genetic and physiological evidence. Circulation 108(24):3042-7. [PubMed: 14638548]  [MGI Ref ID J:104238]

Additional References

Tg(ACTB-DDAH1)1Jpck related

Jacobi J; Maas R; Cordasic N; Koch K; Schmieder RE; Boger RH; Hilgers KF. 2008. Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice. Am J Physiol Heart Circ Physiol 294(2):H1058-66. [PubMed: 18156199]  [MGI Ref ID J:132364]

Jacobi J; Sydow K; von Degenfeld G; Zhang Y; Dayoub H; Wang B; Patterson AJ; Kimoto M; Blau HM; Cooke JP. 2005. Overexpression of dimethylarginine dimethylaminohydrolase reduces tissue asymmetric dimethylarginine levels and enhances angiogenesis. Circulation 111(11):1431-8. [PubMed: 15781754]  [MGI Ref ID J:108993]

Tanaka M; Sydow K; Gunawan F; Jacobi J; Tsao PS; Robbins RC; Cooke JP. 2005. Dimethylarginine dimethylaminohydrolase overexpression suppresses graft coronary artery disease. Circulation 112(11):1549-56. [PubMed: 16144995]  [MGI Ref ID J:118229]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as hemizygotes. Homozygous mice were not propagated because litter size was small.

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
	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.

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Ordering and Purchasing Information

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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

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

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.”

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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.