Strain Name:

B6;SJL-Tg(Tagln-tTA)1Mrab Tg(tetO-Mcpt1)1Mrab/J

Stock Number:

008082

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
Common Names: SM22a-tTA/TRE-RVCH-HA;    
These SM22a-tTA/TRE-RVCH-HA bi-transgenic mice allow targeted overexpression or Tet-Off conditional expression of vascular chymase in smooth muscle cells, and may be useful in studying the role of elevated chymase activity in systemic hypertension and cardiovascular disease.

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 Stock; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator Marlene Rabinovitch,   Stanford University School of Medicine

Description
Hemizygous tTA+/RVCH+ (or SM22a-tTA/TRE-RVCH-HA) mice are viable and fertile, harboring two transgenes using the Tet-Off system. The SM22a-tTA transgene has the 3 kb SM22alpha promoter directing expression of the tetracycline transactivator gene (tTA) to vascular smooth muscle cells (SMCs). The TRE-RVCH-HA transgene has the tetracycline-responsive element (TRE; also called tet-operator or tetO) controlling expression of a rat vascular chymase-hemagglutinin tag (RVCH-HA) fusion gene. In the absence of tetracycline (or its analog doxycycline (dox)), the SM22alpha promoter limits RVCH-HA fusion protein expression to vascular SMCs. This RVCH overexpression results in hypertension. Because this binary transgenic system also allows for a second level of control, i.e. addition of dox, expression of the RVCH-HA fusion protein can be completely abolished; reversing the hypertension phenotype. These SM22a-tTA/TRE-RVCH-HA bi-transgenic mice allow targeted overexpression or Tet-Off conditional expression of vascular chymase in smooth muscle cells, and may be useful in studying the role of elevated chymase activity in systemic hypertension and cardiovascular disease.

Development
These mice harbor two transgenes using the Tet-Off system; SM22a-tTA and TRE-RVCH-HA. The SM22a-tTA transgene was designed with the 3 kb SM22alpha (transgelin or Tagln) promoter fragment upstream of the tetracycline transactivator gene (tTA). This construct was used to create transgenic mice on a C57BL/6 genetic background. The TRE-RVCH-HA transgene was designed with the tetracycline-responsive element (TRE; also called tet-operator or tetO) upstream of a rat vascular chymase (RVCH or Mcpt1) gene (modified such that a human influenza hemagglutinin (HA) tag is added to the C terminus of mature RVCH protein). This construct was used to create transgenic mice on an "SJL/B6" genetic background. These mice were next backcrossed to C57BL/6 mice for two to three generations and subsequently bred with the SM22a-tTA transgenic mice to generate bi-transgenic offspring (SM22a-tTA/TRE-RVCH-HA). These SM22a-tTA/TRE-RVCH-HA mice were maintained on a mixed SJL and C57BL/6 genetic background by breeding to wild-type siblings for at least 16 generations prior to arrival at The Jackson Laboratory. Upon arrival, these mice may have been bred with B6SJLF1/J (Stock No. 100012) hybrid mice to maintain the colony.

Control Information

  Control
   Noncarrier
   100012 B6SJLF1/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Tagln
006878   B6.129S6-Taglntm2(cre)Yec/J
006875   FVB/N-Tg(Tagln-rtTA)E1Jwst/J
004746   STOCK Tg(Tagln-cre)1Her/J
View Strains carrying other alleles of Tagln     (3 strains)

View Strains carrying other alleles of tTA     (22 strains)

Strains carrying other alleles of tetO
006361   B6.Cg-Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/J
003762   B6.Cg-Tg(tetFosb)4468Nes/J
007051   B6.Cg-Tg(tetO-APPSwInd)102Dbo/J
007052   B6.Cg-Tg(tetO-APPSwInd)107Dbo/J
007049   B6.Cg-Tg(tetO-APPSwInd)885Dbo/J
007618   B6.Cg-Tg(tetO-Arntl)1Jt/J
008277   B6.Cg-Tg(tetO-Clockm1Jt)CL57Jt/J
008468   B6.Cg-Tg(tetO-DTA)1Gfi/J
006234   B6.Cg-Tg(tetO-cre)1Jaw/J
005738   B6.FVB-Tg(tetO-EGFP,-Tgfbr2)8Mcle/J
002709   B6;C3-Tg(TettTALuc)1Dgs/J
008344   B6;DBA-Tg(Fos-tTA,Fos-EGFP*)1Mmay Tg(tetO-lacZ,tTA*)1Mmay/J
010577   B6;SJL-Tg(tetO-Erbb2*)8-4Jek/J
002621   B6;SJL-Tg(tetop-lacZ)2Mam/J
006004   B6C3-Tg(tetO-APPSwInd)885Dbo/J
006244   C.Cg-Tg(tetO-cre)1Jaw/J
005706   C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J
006618   C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J
008278   C57BL/6J-Tg(tetO-Clock)1Jt/J
010578   FVB-Tg(tetO-Dusp6)1Jmol/J
008685   FVB-Tg(tetO-Kdr*)4377.5Rwng/J
008695   FVB-Tg(tetO-MET)23Rwng/J
006439   FVB-Tg(tetO/CMV-KRAS*G12C)9.1Msmi/J
008244   FVB.Cg-Tg(tetO-cre)1Jaw/J
005941   FVB/N-Tg(tetO-Aurkb,lacZ)41Kra/J
006202   FVB/N-Tg(tetO-BCR/ABL1)2Dgt/J
003315   FVB/N-Tg(tetORo1-lacZ)3Conk/J
005076   NOD.Cg-Tg(tetO-EGFP/FADD)1Doi/DoiJ
006999   STOCK Dbttm1Geh Tg(tTALap)5Bjd Tg(tetO-DBT)A1Geh/J
008755   STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J
008790   STOCK Tg(tetO-DISC1*)1001Plet/J
008168   STOCK Tg(tetO-DTA)1Gfi/J
005104   STOCK Tg(tetO-HIST1H2BJ/GFP)47Efu/J
005699   STOCK Tg(tetO-Ipf1,EGFP)956.6Macd/J
005728   STOCK Tg(tetO-Ipf1,lacZ)958.1Macd/J
006224   STOCK Tg(tetO-cre)1Jaw/J
View Strains carrying other alleles of tetO     (36 strains)

Additional Web Information

Tet Expression Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(Tagln-tTA)1Mrab/0 Tg(tetO-Mcpt1)1Mrab/0

        involves: C57BL/6 * SJL
  • cardiovascular system phenotype
  • abnormal artery morphology (MGI Ref ID J:70031)
    • medial to lumen ratio of mesenteric artery is increased by 93% compared to single transgenic controls; thickening is reversed by doxycycline-induced suppression of transgene expression
    • abnormal aorta morphology (MGI Ref ID J:70031)
      • increase in media to lumen ratio of aorta is observed in binary transgenic mice
  • abnormal vasoconstriction (MGI Ref ID J:70031)
    • endothelium-dependent (methacholine-induced) relaxation in pre-constricted arteries is impaired relative to controls
    • increased vasoconstriction (MGI Ref ID J:70031)
      • isolated mesenteric arteries display significantly enhanced constriction in response to phenylephrine treatment relative to control arteries
  • increased left ventricle weight (MGI Ref ID J:70031)
    • modest increase in left ventricle weight to body weight is observed in transgene expressing mice
  • increased mean arterial blood pressure (MGI Ref ID J:70031)
    • MAP is increased to 103 mm Hg compared to 82 mm Hg in controls
  • increased systolic blood pressure (MGI Ref ID J:70031)
    • increased by an average of 27 mm Hg relative to littermate controls; 24% increase in blood pressure in double mutants is seen compared to single transgenic mice
    • doxycycline treatment to suppress transgene expression completely reverses increase, returning blood pressure to control values
  • cellular phenotype
  • increased cell proliferation (MGI Ref ID J:70031)
    • abundant expression of proliferating cells is observed of medial layer of mesenteric artery in double mutants
  • muscle phenotype
  • abnormal vasoconstriction (MGI Ref ID J:70031)
    • endothelium-dependent (methacholine-induced) relaxation in pre-constricted arteries is impaired relative to controls
    • increased vasoconstriction (MGI Ref ID J:70031)
      • isolated mesenteric arteries display significantly enhanced constriction in response to phenylephrine treatment relative to control arteries
View Research Applications

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

Cardiovascular Research
Hypertension
      normotensive

Research Tools
Cardiovascular Research
      Tetop Tet System
Genetics Research
      Mutagenesis and Transgenesis: Tetop Tet System
Tet Expression Systems
      tTA/rtTA Expressing Strains
      tTA/rtTA Responsive Strains

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Tg(Tagln-tTA)1Mrab
Allele Name transgene insertion 1, Marlene Rabinovitch
Allele Type Transgenic (random, expressed)
Common Name(s) SM22alpha- tTA; tTA+;
Strain of OriginC57BL/6
Site of Expressionvascular smooth muscle cells (SMCs)
Expressed Gene tTA, tetracycline-controlled transactivator, E. coli
The tetracycline-resistance gene (TetR), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). TetR was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). The tetracycline-inhibitable transcription factor is a component of a bigenic system that allows doxycycline (a tetracycline analog) regulatable expression of genes that are under the direction of the tetracycline responsive promoter (TetOp)promoter.
Promoter Tagln, transgelin, mouse, laboratory
Molecular Note Sequence encoding a tetracycline transactivator was adjoined to the smooth muscle cell specific transgelin promoter. The promoter was reported to drive expression in the aorta, but not in the heart, lung, kidney, bladder, intestine, or stomach. [MGI Ref ID J:70031]
 
 
 
Allele Symbol Tg(tetO-Mcpt1)1Mrab
Allele Name transgene insertion 1, Marlene Rabinovitch
Allele Type Transgenic (random, expressed)
Common Name(s) RVCH+; TRE-RVCH-HA;
Site of ExpressionAs the tetracycline-responsive element (TRE; also called tet-operator or tetO) controls expression of the rat vascular chymase-hemagglutinin tag (RVCH-HA) fusion gene, RVCH-HA expression is spatially and temporally dependent upon exposure to tetracycline transactivator (tTA).
Expressed Gene Mcpt1, mast cell protease 1, rat
Promoter tetO, tet operator,
Molecular Note The transgene was designed with the tetracycline-responsive element (TRE; also called tet-operator or tetO) upstream of a rat vascular chymase (RVCH or Mcpt1) gene modified such that a human influenza hemagglutinin (HA) tag is added to the C terminus ofmature RVCH protein. With ddition of dox expression of the RVCH-HA fusion protein can be completely abolished, reversing the hypertension phenotype. [MGI Ref ID J:70031]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(TagIn-tTA)1Mrab, Standard PCR
Tg(tetO-Mcpt1)1Mrab, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Ju H; Gros R; You X; Tsang S; Husain M; Rabinovitch M. 2001. Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice. Proc Natl Acad Sci U S A 98(13):7469-74. [PubMed: 11416217]  [MGI Ref ID J:70031]

Additional References

Tg(Tagln-tTA)1Mrab related

El-Bizri N; Wang L; Merklinger SL; Guignabert C; Desai T; Urashima T; Sheikh AY; Knutsen RH; Mecham RP; Mishina Y; Rabinovitch M. 2008. Smooth muscle protein 22alpha-mediated patchy deletion of Bmpr1a impairs cardiac contractility but protects against pulmonary vascular remodeling. Circ Res 102(3):380-8. [PubMed: 18079409]  [MGI Ref ID J:141529]

Gros R; Afroze T; You XM; Kabir G; Van Wert R; Kalair W; Hoque AE; Mungrue IN; Husain M. 2003. Plasma membrane calcium ATPase overexpression in arterial smooth muscle increases vasomotor responsiveness and blood pressure. Circ Res 93(7):614-21. [PubMed: 12933703]  [MGI Ref ID J:128144]

Health & husbandry

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.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, mice hemizygous for both transgenes may be bred together, to wildtype siblings, or to B6SJLF1/J (Stock No. 100012) inbred mice. It may be useful to maintain mice on doxycycline-treated water to avoid hypertension or other incidental effects of tTA or RVCH expression.

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
Animals Provided

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.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
Animals Provided

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.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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).

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Control
   Noncarrier
   100012 B6SJLF1/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.

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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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Use of the Tet-System may require a license, see Licenses for Strains Using TET-System Technology.

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