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Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N7p Donating Investigator Katya Ravid, Boston University School of Medicine Description
Transgenic mice are viable, fertile, normal in size, and do not display any behavioral abnormalities. Transgenic tetracycline-controlled transactivator protein (tTA) expression is limited to megakaryocytes by the rat chemokine (C-X-C motif) ligand 4 (Cxcl4; formerly called platelet factor four (Pf4)) promoter. When bred to mice carrying a gene of interest coupled to a tetracycline-responsive promoter element (TRE; tetO), expression of the target gene is induced specifically in megakaryocytes. Administration of tetracycline/doxycycline sequesters the transgenic protein, and prevents expression of the TRE-regulated target gene.This mouse originally was designed to be bred with Tg(tetO-Aurkb,lacZ)41Kra (see Stock No. 005941); a transgenic mouse with a bidirectional tetO promoter controlling a mitotic regulator gene (aurora kinase B) and a beta-galactosidase reporter. Megakaryocytes and platelet cells from the bitransgenic offspring show inducible and reversible beta-galactosidase expression. Further, megakaryocytes inducibly express Aurora kinase-B mRNA (but not protein) with a modest effect on megakaryocyte ploidy and no effect on platelet quantity. These mice may be useful in studies of megakaryocyte/platelet lineage cell function, including migration following injury/insult and overexpression of thrombotic agents.
Development
A transgenic construct was designed using the promoter region from rat chemokine (C-X-C motif) ligand 4 (Cxcl4; formerly called platelet factor four (Pf4)) to direct expression of the tetracycline-regulated transactivator, tTA. The construct was injected into fertilized FVB/NJ eggs which were subsequently implanted into pseudopregnant foster mothers. Founder line 42 was obtained and bred to FVB/NJ mice for 3 generations. Transgenic mice were interbred for 5 generations.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of tTA
007004 B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ 003767 B6.Cg-Tg(Eno2tTA)5021Nes/J 003763 B6.Cg-Tg(Eno2tTA)5030Nes/J 005964 B6.Cg-Tg(GFAP-tTA)110Pop/J 002618 B6.Cg-Tg(MMTVtTA)1Mam/J 006361 B6.Cg-Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/J 003563 B6.Cg-Tg(tTALap)5Bjd/J 002709 B6;C3-Tg(TettTALuc)1Dgs/J 003010 B6;CBA-Tg(Camk2a-tTA)1Mmay/J 008082 B6;SJL-Tg(Tagln-tTA)1Mrab Tg(tetO-Mcpt1)1Mrab/J 005625 FVB-Tg(Pcp2-tTA)3Horr/J 003170 FVB.Cg-Tg(Myh6-tTA)6Smbf/J 006209 FVB.Cg-Tg(Tal1-tTA)19Dgt/J 004937 NOD.Cg-Tg(Ins2-tTA)1Doi/DoiJ 006999 STOCK Dbttm1Geh Tg(tTALap)5Bjd Tg(tetO-DBT)A1Geh/J 003272 STOCK Tg(tTALap)5Bjd/J 003271 STOCK Tg(tTAhCMV)3Bjd/J 003275 STOCK Tg(tetL)1Bjd/J 003274 STOCK Tg(tetNZL)2Bjd/J View Strains carrying other alleles of tTA (19 strains)
Tet Expression Systems
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
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(PF4-tTA/VP16)42Kra/0 Tg(tetO-Aurkb,lacZ)41Kra/0
FVB/NJ-Tg(tetO-Aurkb,lacZ)41Kra Tg(PF4-tTA/VP16)42Kra
- homeostasis/metabolism phenotype
- abnormal platelet physiology (MGI Ref ID J:104239)
- after LPS treatment, mice show accumulation of platelets in the liver and lungs in the induced (doxycycline removed) state
- hematopoietic system phenotype
- abnormal platelet physiology (MGI Ref ID J:104239)
- after LPS treatment, mice show accumulation of platelets in the liver and lungs in the induced (doxycycline removed) state
- abnormal thrombopoiesis (MGI Ref ID J:104239)
- induced mice show no increase in platelet number compared to control
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Research Tools
Tet Expression Systems (tTA/rtTA Expressing Strains)
| Allele Symbol | Tg(PF4-tTA/VP16)42Kra | ||
|---|---|---|---|
| Allele Name | transgene insertion 42, Katya Ravid | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | PF4-tTA-VP16; | ||
| Strain of Origin | FVB/NJ | ||
| ES Cell Line Strain | 129 | ||
| Site of Expression | Expresses tTA in megakaryocytes. | ||
| 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 | Pf4, platelet factor 4, rat | ||
| Molecular Note | The rat platelet factor 4 (RP4) promoter was cloned into the tTA-containing plasmid, replacing the existing CMV promoter. The promoter will drive expression of the transactivator tTA fused to the viral coactivator VP16. Expression is repressed with administration of doxycycline and is induced by removal of doxycycline from the diet of the mice.The transgene also contains 1.7 kb of the 3'end of the human beta-globin gene including the 3' intron and polyadenylation signal to permit stable RNA production inmice. A stop codon in the transgene prevents translation of beta-globin into the protein. [MGI Ref ID J:104239] | ||
Genotyping Protocols
Tg(tTA), MCA, vers. 4
Tg(tTA), STD PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
Nguyen HG; Yu G; Makitalo M; Yang D; Xie HX; Jones MR; Ravid K. 2005. Conditional overexpression of transgenes in megakaryocytes and platelets in vivo. Blood 106(5):1559-64. [PubMed: 15890684] [MGI Ref ID J:104239]
Zhang Y; Nagata Y; Yu G; Nguyen HG; Jones MR; Toselli P; Jackson CW; Tatsuka M; Todokoro K; Ravid K. 2004. Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1-deregulated expression. Blood 103(10):3717-26. [PubMed: 14751927] [MGI Ref ID J:90544]
Currently there no information available for this strain. This may be due to the supply level of this strain.
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| 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. | ||
Purchasing Information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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