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| 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 inducible deletion of specific groups of cells. | ||||||||||||||||||
- Description
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Description
Strain Information
Type Congenic; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 19-NOV-09 Species laboratory mouse Generation N5F2 (18-NOV-09) Donating Investigator IMR Colony, The Jackson Laboratory 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.
When bred to a strain expressing tTA in pancreatic beta cells (see Stock No. 008250 for example), this mutant mouse strain may be useful in studies of diabetes and beta cell regeneration.
When bred to a strain expressing tTA in pancreatic beta cells (see Stock No. 008250) as well as a strain with a tamoxifen inducible Cre recomibinase (see Stock No. 008122 and a strain with a cre inducible alkaline phosphatase (see Stock No. 003919 , this mutant mouse strain may be useful in studies of diabetes and beta cell regeneration.
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 (as Stock No. 008168). Upon arrival, some mice were backcrossed to C57BL/6J for at least 5 generations to generate this congenic strain (Stock No. 008468).
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(tetO-DTA)1Gfi allele
008755 STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J 008168 STOCK Tg(tetO-DTA)1Gfi/J View Strains carrying Tg(tetO-DTA)1Gfi (2 strains)
008617 B6(A)-Tg(OPN1LW-DT)1Mame/J 006576 B6.FVB-Tg(GNAT2-Dta)98Wwk/J 002384 FVB/N-Tg(UcpDta)1Kz/J
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Tg(CAG-Bgeo/ALPP)1Lbe/0 Tg(Ins2-cre/Esr1)1Dam/0 Tg(Ins2-rtTA)2Efr/0 Tg(tetO-DTA)1Gfi/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
- digestive/alimentary phenotype
- increased pancreatic beta cell number (MGI Ref ID J:127412)
- tamoxifen injections during last 10 days of doxycycline treatment labels surviving beta cells with human placental alkaline phosphatase; labeling results indicate that majority or all regenerated beta cells are derived from surviving beta cells, rather than from non-beta cells or stem cells
- endocrine/exocrine gland phenotype
- increased pancreatic beta cell number (MGI Ref ID J:127412)
- tamoxifen injections during last 10 days of doxycycline treatment labels surviving beta cells with human placental alkaline phosphatase; labeling results indicate that majority or all regenerated beta cells are derived from surviving beta cells, rather than from non-beta cells or stem cells
- homeostasis/metabolism phenotype
- hyperglycemia (MGI Ref ID J:127412)
- treatment of newborn mice with doxycycline for 45 days results in diabetes development
Tg(Ins2-rtTA)2Efr/0 Tg(tetO-DTA)1Gfi/0
involves: C57BL/6 * CBA
- endocrine/exocrine gland phenotype
- *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:127412)
- average size of regenerating beta cells is same as original cells
- abnormal pancreas morphology (MGI Ref ID J:127412)
- pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels
- abnormal pancreatic beta cell morphology (MGI Ref ID J:127412)
- frequency of insulin-positive, glucagons-positive beta cells increases from 1:5500 in controls to 1:1000 beta cells in diabetic transgenic mice
- permitting doxycycline-treated mice to recover in presence of immunosupressants Sirolimus and Tacrolimus (SirTac) significantly reduces beta cell proliferation and beta cell mass does not increase as it does in absence of immunosupressants; blood glucose levels in treated mice fail to normalize as they do in controls treated with SirTac
- decreased pancreatic beta cell number (MGI Ref ID J:127412)
- 70-80% of beta cells are lost in doxycycline-treated 5-week old double-transgenic mice relative to controls
- similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
- increased pancreatic beta cell number (MGI Ref ID J:127412)
- rate of beta cell apoptosis in recovering mice is not different from controls, but beta cell proliferation is increased 2-3-fold within 48 hours of onset of beta cell ablation; this increased proliferation rate is maintained for several weeks
- disorganized pancreatic islets (MGI Ref ID J:127412)
- treatment of four-week old mice with doxycycline for 1 week results in severely disrupted islet architecture with non-beta cells at the core of shriveled islets rather than beta cells
- after withdrawal of doxycycline, normalization of islet architecture occurs in ~90% of islets
- digestive/alimentary phenotype
- abnormal pancreas morphology (MGI Ref ID J:127412)
- pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels
- abnormal pancreatic beta cell morphology (MGI Ref ID J:127412)
- frequency of insulin-positive, glucagons-positive beta cells increases from 1:5500 in controls to 1:1000 beta cells in diabetic transgenic mice
- permitting doxycycline-treated mice to recover in presence of immunosupressants Sirolimus and Tacrolimus (SirTac) significantly reduces beta cell proliferation and beta cell mass does not increase as it does in absence of immunosupressants; blood glucose levels in treated mice fail to normalize as they do in controls treated with SirTac
- decreased pancreatic beta cell number (MGI Ref ID J:127412)
- 70-80% of beta cells are lost in doxycycline-treated 5-week old double-transgenic mice relative to controls
- similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
- increased pancreatic beta cell number (MGI Ref ID J:127412)
- rate of beta cell apoptosis in recovering mice is not different from controls, but beta cell proliferation is increased 2-3-fold within 48 hours of onset of beta cell ablation; this increased proliferation rate is maintained for several weeks
- disorganized pancreatic islets (MGI Ref ID J:127412)
- treatment of four-week old mice with doxycycline for 1 week results in severely disrupted islet architecture with non-beta cells at the core of shriveled islets rather than beta cells
- after withdrawal of doxycycline, normalization of islet architecture occurs in ~90% of islets
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype (MGI Ref ID J:127412)
- peripheral insulin sensitivity after beta cell regeneration is similar to controls after doxycycline withdrawal, beta cell mass in transgenic mice increases to levels comparable to wild-type
- improved glucose tolerance (MGI Ref ID J:127412)
- after more than 8 months without doxycycline, glucose tolerance starts to recover
- similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
- mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
- increased circulating glucose level (MGI Ref ID J:127412)
- blood glucose levels of treated mice are elevated to 300-600 mg/dl making the mice overtly diabetic; after withdrawal of doxycycline, blood glucose levels return to normal level
- mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
- hyperglycemia (MGI Ref ID J:127412)
- blood glucose levels are elevated to 300-600 mg/dl; after doxycycline withdrawal, remission of hyperglycemia occurs such that fed and fasting glucose levels normalize
- mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
- cellular phenotype
- increased apoptosis (MGI Ref ID J:127412)
- widespread pancreatic beta cell apoptosis is seen within 48 hours of doxycycline treatment of double-transgenic mice, but no apoptosis is observed in single transgenic littermates
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
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
Toxicology Research
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
Tg(tetO-DTA)1Gfi, QPCR
Tg(tetO-DTA)1Gfi, Standard PCR
tg(teto-DTA)1Gfi/j, Melt Curve Analysis
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]
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 & Husbandry Mutant mice were bred to C57BL/6J mice for may generations to establish this congenic strain. When maintaining the live congenic colony, homozygous mice may be bred together. Of note, homozygosity was determined by qPCR. Mating System Homozygote x Homozygote (Female x Male) 19-NOV-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 |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $209.90 Female or Male Homozygous for Tg(tetO-DTA)1Gfi
Pairs /Price (US dollars $) Pair Genotype $419.80 Homozygous for Tg(tetO-DTA)1Gfi x Homozygous for Tg(tetO-DTA)1Gfi
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $272.90 Female or Male Homozygous for Tg(tetO-DTA)1Gfi
Pairs /Price (US dollars $) Pair Genotype $545.80 Homozygous for Tg(tetO-DTA)1Gfi x Homozygous for Tg(tetO-DTA)1Gfi
Additional Supply Details
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Supply Details
| Standard Supply | Repository-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. |
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| Supply Notes |
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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. | ||
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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.Ordering and Purchasing Information
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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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