Strain Name:

STOCK Tg(tetO-DTA)1Gfi/J

Stock Number:

008168

Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
These tet-DTA mice express diphtheria toxin A (DTA) under the control of a tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) and a cytomegalovirus minimal promoter, and may be useful in generating bi-transgenic mutant mice for the reversible, inducible deletion of specific groups of cells.

Description

Strain Information

Type Mutant Stock; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   05-FEB-09
Specieslaboratory mouse
GenerationF?+F1 (02-JAN-09)
 
Donating Investigator Douglas Melton,   Harvard University

Description
These tet-DTA transgenic mice express diphtheria toxin A (DTA) under the control of a tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) and a cytomegalovirus minimal promoter. When bred with another mouse expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), tissue diphtheria toxin A expression can be regulated with the tetracycline analog doxycycline (dox) in the resulting double mutant offspring. These tet-DTA mice may be useful in generating bi-transgenic mutant mice for the reversible, inducible deletion of specific groups of cells.

For example, when bred to a strain expressing tTA in cardiac myocytes (see Stock No. 003170 for example), this mutant mouse strain may be useful in studies of human cardiomyopathies.

Development
The tet-DTA transgene was designed with a diphtheria toxin A (DTA) sequence under the control of heptamerized tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) sequences and a cytomegalovirus minimal promoter. This transgene was injected into fertilized B6CBAF2 mouse eggs. Founder animals were bred to outbred ICR mice and then made homozygous prior to arrival at The Jackson Laboratory.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(tetO-DTA)1Gfi allele
008468   B6.Cg-Tg(tetO-DTA)1Gfi/J
008755   STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J
View Strains carrying   Tg(tetO-DTA)1Gfi     (2 strains)

Strains carrying other alleles of Dta
008617   B6(A)-Tg(OPN1LW-DT)1Mame/J
006576   B6.FVB-Tg(GNAT2-Dta)98Wwk/J
002384   FVB/N-Tg(UcpDta)1Kz/J
View Strains carrying other alleles of Dta     (3 strains)

View Strains carrying other alleles of tetO     (34 strains)

Additional Web Information

Introduction to Cre-lox technology
Tet Expression Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
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Tg(Myh6-tTA)6Smbf/0 Tg(tetO-DTA)1Gfi/0

        involves: C57BL/6 * CBA
  • lethality-prenatal/perinatal
  • embryonic lethality during organogenesis (MGI Ref ID J:128617)
    • in absence of maternal supplementation with tetracycline (Tc) during gestation, no binary (or double) transgenic offspring are born, whereas gestational or perinatal suppressive Tc treatment results in Mendelian numbers of binary offspring (22%)
    • genotypic analysis at times throughout gestation show that death of double transgenic embryos occurs between 10.5 days post conception (dpc) and fetal day 19
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:128617)
    • when Tc treatment is withdrawn after birth, mortality results with median survival time of 37 days (earliest time of death is 12 days after withdrawal of Tc, latest death is 77 days); death occurs suddenly with no indication of illness
  • cardiovascular system phenotype
  • abnormal heart atrium morphology (MGI Ref ID J:128617)
    • atrial tissue destruction is seen in some hearts
  • abnormal heart ventricle morphology (MGI Ref ID J:128617)
    • ventricles show patchy fibrosis following Tc withdrawal
    • dilated heart ventricles (MGI Ref ID J:128617)
      • in some hearts, prominent ventricular dilatation is observed following Tc withdrawal
  • abnormal impulse conducting system conduction (MGI Ref ID J:128617)
    • at 1 month after tetracycline withdrawal, a subset of isolated-perfused hearts display markedly disturbed activation profiles, with either disorganized conduction or evidence of block during pacing
    • majority of even mildly diseased hearts are arrhythmogenic
  • cardiac fibrosis (MGI Ref ID J:128617)
    • ventricles show mild patchy fibrosis to severe fibrosis following Tc withdrawal
  • decreased myocardial fiber number (MGI Ref ID J:128617)
    • hearts show evidence of mild to severe myocyte loss
  • increased cardiomyocyte apoptosis (MGI Ref ID J:128617)
    • some hearts display severe cell loss following tetracycline withdrawal
  • irregular heartbeat (MGI Ref ID J:128617)
    • following Tc withdrawal, a variety of arrhythmias are detected in double transgenic mice which show increased propensity to develop reentrant tachycardia, including atrial fibrillation, pauses, and complex ventricular ectopy such as runs of ventricular tachycardia
    • majority of even mildly diseased hearts are arrhythmogenic
    • atrial fibrillation (MGI Ref ID J:128617)
      • following tetracycline withdrawal, atrial fibrillation occurs in some mice
  • ventricular tachycardia (MGI Ref ID J:128617)
    • at 1 month after Tc withdrawal, most isolated-perfused hearts display either spontaneous or inducible ventricular tachycardia, including both sustained and nonsustained runs of ventricular tachycardia with some episodes lasting
  • muscle phenotype
  • decreased myocardial fiber number (MGI Ref ID J:128617)
    • hearts show evidence of mild to severe myocyte loss
  • increased cardiomyocyte apoptosis (MGI Ref ID J:128617)
    • some hearts display severe cell loss following tetracycline withdrawal
  • homeostasis/metabolism phenotype
  • atrial thrombosis (MGI Ref ID J:128617)
    • mural thrombus formation is prominent in atrial tissue in some animals following Tc withdrawal
View Research Applications

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

Cell Biology Research
Genes Regulating Growth and Proliferation

Neurobiology Research
Tet Expression System
      tTA/rtTA Responsive Strains

Research Tools
Cancer Research
      Tetop Tet System
Cardiovascular Research
      Tetop Tet System
Cell Biology Research
Genetics Research
      Mutagenesis and Transgenesis: Tetop Tet System
Neurobiology Research
      Tetop Tet System
Reproductive Biology Research
      Tetop Tet System
Tet Expression Systems
      tTA/rtTA Responsive Strains

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Tg(tetO-DTA)1Gfi
Allele Name transgene insertion 1, Glenn I Fishman
Allele Type Transgenic (random, expressed)
Common Name(s) tet-DTA; tetODTA/+;
Strain of Origin(C57BL/6 x CBA)F2
Expressed Gene Dta, Diphtheria toxin A chain,
Brown fat specific expression of the A-chain of diptheria toxin (DTA) resulting in ablation of brown fat.
Promoter tetO, tet operator,
Molecular Note A transgenic construct was created, containing diphtheria toxin A sequence (DTA) under the control of heptamerized tetracycline operator, tetO sequences fused to a cytomegalovirus minimal promoter. [MGI Ref ID J:128617]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Prkdcscid, Pyrosequencing
tg(teto-DTA)1Gfi/j, Melt Curve Analysis
Tg(tTA), Melt Curve Analysis
Tg(tTA), QPCR
Tg(tetO-DTA)1Gfi, QPCR
Tg(tetO-DTA)1Gfi, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Lee P; Morley G; Huang Q; Fischer A; Seiler S; Horner JW; Factor S; Vaidya D; Jalife J; Fishman GI. 1998. Conditional lineage ablation to model human diseases. Proc Natl Acad Sci U S A 95(19):11371-6. [PubMed: 9736743]  [MGI Ref ID J:128617]

Additional References

Stanger BZ; Tanaka AJ; Melton DA. 2007. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445(7130):886-91. [PubMed: 17259975]  [MGI Ref ID J:118596]

Tg(tetO-DTA)1Gfi related

Nir T; Melton DA; Dor Y. 2007. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest 117(9):2553-61. [PubMed: 17786244]  [MGI Ref ID J:127412]

Stanger BZ; Tanaka AJ; Melton DA. 2007. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445(7130):886-91. [PubMed: 17259975]  [MGI Ref ID J:118596]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together. Of note, homozygosity was determined by qPCR.
Mating SystemHomozygote x Homozygote         (Female x Male)   05-FEB-09
Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice (US dollars $)GenderGenotypes Provided
Individual Mouse $209.90Female or MaleHomozygous for Tg(tetO-DTA)1Gfi
Pairs /Price (US dollars $)Pair Genotype
$419.80Homozygous for Tg(tetO-DTA)1Gfi x Homozygous for Tg(tetO-DTA)1Gfi

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice (US dollars $)GenderGenotypes Provided
Individual Mouse $272.90Female or MaleHomozygous for Tg(tetO-DTA)1Gfi
Pairs /Price (US dollars $)Pair Genotype
$545.80Homozygous for Tg(tetO-DTA)1Gfi x Homozygous for Tg(tetO-DTA)1Gfi

Additional Supply Details

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.
Supply Notes

Control Information

  Control
   None Available
 
  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


General Terms and Conditions


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

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