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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. | ||||||||||||||||||||||
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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 N5F6 (12-JUL-11)
Generation DefinitionsDonating 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 008755 STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J 008168 STOCK Tg(tetO-DTA)1Gfi/J
008755 STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J 008168 STOCK Tg(tetO-DTA)1Gfi/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/ERT)1Dam/0 Tg(Ins2-rtTA)2Efr/0 Tg(tetO-DTA)1Gfi/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
- endocrine/exocrine gland phenotype
- increased pancreatic beta cell number
- 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 (MGI Ref ID J:127412)
- homeostasis/metabolism phenotype
- hyperglycemia
- treatment of newborn mice with doxycycline for 45 days results in diabetes development (MGI Ref ID J:127412)
Tg(Ins2-rtTA)2Efr/0 Tg(tetO-DTA)1Gfi/0
involves: C57BL/6 * CBA
- endocrine/exocrine gland phenotype
- *normal* endocrine/exocrine gland phenotype
- average size of regenerating beta cells is same as original cells (MGI Ref ID J:127412)
- abnormal pancreas morphology
- pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels (MGI Ref ID J:127412)
- abnormal pancreatic beta cell morphology
- frequency of insulin-positive, glucagons-positive beta cells increases from 1:5500 in controls to 1:1000 beta cells in diabetic transgenic mice (MGI Ref ID J:127412)
- 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 (MGI Ref ID J:127412)
- decreased pancreatic beta cell number
- 70-80% of beta cells are lost in doxycycline-treated 5-week old double-transgenic mice relative to controls (MGI Ref ID J:127412)
- 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 (MGI Ref ID J:127412)
- increased pancreatic beta cell number
- 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 (MGI Ref ID J:127412)
- disorganized pancreatic islets
- 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 (MGI Ref ID J:127412)
- after withdrawal of doxycycline, normalization of islet architecture occurs in ~90% of islets (MGI Ref ID J:127412)
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
- 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 (MGI Ref ID J:127412)
- improved glucose tolerance
- after more than 8 months without doxycycline, glucose tolerance starts to recover (MGI Ref ID J:127412)
- 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 (MGI Ref ID J:127412)
- 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 (MGI Ref ID J:127412)
- increased circulating glucose level
- 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 (MGI Ref ID J:127412)
- 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 (MGI Ref ID J:127412)
- hyperglycemia
- 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 (MGI Ref ID J:127412)
- 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 (MGI Ref ID J:127412)
- cellular phenotype
- increased apoptosis
- 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 (MGI Ref ID J:127412)
Tg(Myh6-tTA)6Smbf/0 Tg(tetO-DTA)1Gfi/0
involves: C57BL/6 * CBA
- mortality/aging
- complete lethality throughout fetal growth and development
- 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%) (MGI Ref ID J:128617)
- 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 (MGI Ref ID J:128617)
- partial embryonic lethality during organogenesis
- 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%) (MGI Ref ID J:128617)
- 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 (MGI Ref ID J:128617)
- premature death
- 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 (MGI Ref ID J:128617)
- cardiovascular system phenotype
- abnormal heart atrium morphology
- atrial tissue destruction is seen in some hearts (MGI Ref ID J:128617)
- abnormal heart ventricle morphology
- ventricles show patchy fibrosis following Tc withdrawal (MGI Ref ID J:128617)
- dilated heart ventricle
- in some hearts, prominent ventricular dilatation is observed following Tc withdrawal (MGI Ref ID J:128617)
- abnormal impulse conducting system conduction
- 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 (MGI Ref ID J:128617)
- majority of even mildly diseased hearts are arrhythmogenic (MGI Ref ID J:128617)
- cardiac fibrosis
- ventricles show mild patchy fibrosis to severe fibrosis following Tc withdrawal (MGI Ref ID J:128617)
- decreased myocardial fiber number
- hearts show evidence of mild to severe myocyte loss (MGI Ref ID J:128617)
- increased cardiomyocyte apoptosis
- some hearts display severe cell loss following tetracycline withdrawal (MGI Ref ID J:128617)
- irregular heartbeat
- 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 (MGI Ref ID J:128617)
- majority of even mildly diseased hearts are arrhythmogenic (MGI Ref ID J:128617)
- atrial fibrillation
- following tetracycline withdrawal, atrial fibrillation occurs in some mice (MGI Ref ID J:128617)
- ventricular tachycardia
- 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
J:128617) - muscle phenotype
- decreased myocardial fiber number
- hearts show evidence of mild to severe myocyte loss (MGI Ref ID J:128617)
- increased cardiomyocyte apoptosis
- some hearts display severe cell loss following tetracycline withdrawal (MGI Ref ID J:128617)
- homeostasis/metabolism phenotype
- atrial thrombosis
- mural thrombus formation is prominent in atrial tissue in some animals following Tc withdrawal (MGI Ref ID J:128617)
- cellular phenotype
- increased cardiomyocyte apoptosis
- some hearts display severe cell loss following tetracycline withdrawal (MGI Ref ID J:128617)
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
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 provided by MGI
| 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, | ||
| 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 provided by MGI
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]
Additional References
Tg(tetO-DTA)1Gfi relatedPorat S; Weinberg-Corem N; Tornovsky-Babaey S; Schyr-Ben-Haroush R; Hija A; Stolovich-Rain M; Dadon D; Granot Z; Ben-Hur V; White P; Girard CA; Karni R; Kaestner KH; Ashcroft FM; Magnuson MA; Saada A; Grimsby J; Glaser B; Dor Y. 2011. Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab 13(4):440-9. [PubMed: 21459328] [MGI Ref ID J:172243]
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
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $225.00 Female or Male Homozygous for Tg(tetO-DTA)1Gfi
Pairs /Price (US dollars $) Pair Genotype $450.00 Homozygous for Tg(tetO-DTA)1Gfi x Homozygous for Tg(tetO-DTA)1Gfi Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $292.50 Female or Male Homozygous for Tg(tetO-DTA)1Gfi
Pairs /Price (US dollars $) Pair Genotype $585.00 Homozygous for Tg(tetO-DTA)1Gfi x Homozygous for Tg(tetO-DTA)1Gfi Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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|
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Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| 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 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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