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Strain Name:

STOCK Tg(tetO-DTA)1Gfi/J

Stock Number:

008168

Availability:

Under Development for Distribution Colony

To register your interest in this strain go to the Strain Interest Form.
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Additional Licensing and Use Restrictions

Genes & Alleles   Dta;   Tg(tetO-DTA)1Gfi;   tetO;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Mating SystemHemizygote x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Douglas Melton,   Harvard University
GenerationF?+ (21-JUL-08)

Strain 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.

Strain 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.

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
  • increased heart rate (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
  • 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
  • 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

Gene & Allele Details

Allele Symbol Tg(tetO-DTA)1Gfi
Allele Name transgene insertion 1, Glenn I Fishman
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 Protocols

Tg(tetO-DTA)1Gfi

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous mice may be bred together, or with wildtype siblings. The donating investigator reports they breed homozygous mice together.
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Dta
006576   B6.FVB-Tg(GNAT2-Dta)98Wwk/J
002384   FVB/N-Tg(UcpDta)1Kz/J
View Strains carrying other alleles of Dta     (2 strains)

View Strains carrying other alleles of tetO     (27 strains)

Additional Web Information

Tet Expression Systems

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)

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

Price and Supply Information

Strain Name: STOCK Tg(tetO-DTA)1Gfi/J
Stock Number: 008168
 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date: 29-SEP-08

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development

Supply Details

Standard SupplyUnder Development for Distribution Colony
Supply Notes This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

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

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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