Description

Strain Information

Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Noncarrier x Hemizygote         (Female x Male)   03-DEC-08 Species laboratory mouse Generation N5F1 (04-MAY-09)   Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Transgenic Pax8-rtTA mice are viable and fertile. These mice express an optimized reverse tetracycline-controlled transactivator (rtTA2^S-M2) protein under the control of the murine Pax8 promoter, which directs expression to proximal and distal tubules and the collecting duct system of both embryonic and adult kidney. The rtTA2^S-M2 variant of rtTA contains five amino acid changes in the TetR moiety (S12G, E19G, A56P, D148E, and H179R) and a synthetic optimized transactivating domain, resulting in reduced basal activity and enhanced doxycycline sensitivity compared to wild-type rtTA. When mated to a second strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (TRE or tetO), expression of the target gene in kidney cells is induced with administration of the tetracycline analog, doxycycline (dox). These Pax8-rtTA mice provide a Tet-On tool that allows the inducible expression of genes in renal tubular epithelial cells, and may be useful in studying renal disorders such as fibrosis or polycystic kidney disease, renal cancer, and Tuberous Sclerosis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The Pax8-rtTA construct was designed to contain an optimized rtTA variant (rtTA2s-M2) cDNA and SV40 polyA sequence replaced at the endogenous ATG translational start site of a murine Pax8 sequence. This 6.6 kb transgene was microinjected into the pronucleus of one-cell fertilized mouse embryos obtained from superovulated F2 (C57BL/6 x DBA) females, which were then implanted into pseudopregnant foster mice. Founder mice were bred to C57BL/6 mice, and the resulting transgenic offspring were bred together for many generations prior to arrival at The Jackson Laboratory. Upon arrival, some mice were backcrossed to C57BL/6J for at least 5 generations to generate this congenic strain (Stock No. 007176). The Pax8-rtTA construct integrated approximately five copies in a head-to-tail orientation within a mouse L1 line repetitive element (which are located throughout the genome).

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of rtTA

006965	B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae/J
005670	B6.Cg-Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
006235	B6.Cg-Tg(SFTPC-rtTA)5Jaw/J
006232	B6.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
006911	B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm2(tetO-Pou5f1)Jae/J
007678	B6;SJL-Tg(KRT14-rtTA)208Jek/J
010576	B6;SJL-Tg(MMTV-rtTA)4-1Jek/J
006245	C.Cg-Tg(SFTPC-rtTA)5Jaw/J
006242	C.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
008099	FVB-Tg(KRT14-rtTA)F42Efu/J
004127	FVB-Tg(Nes-rtTA)306Rvs/J
006225	FVB.Cg-Tg(SFTPC-rtTA)5Jaw/J
006222	FVB.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
008202	FVB/N-Tg(NPHS2-rtTA2*M2)1Jbk/J
006875	FVB/N-Tg(Tagln-rtTA)E1Jwst/J
004602	NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ
005734	NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ
005572	STOCK Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
008755	STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J
008250	STOCK Tg(Ins2-rtTA)2Efr/J
005493	STOCK Tg(Tek-rtTA,TRE-lacZ)1425Tpr/J
003273	STOCK Tg(rtTAhCMV)4Bjd/J

View Strains carrying other alleles of rtTA     (22 strains)

Additional Web Information

Tet Expression Systems

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      kidney

Endocrine Deficiency Research
Kidney Defects

Internal/Organ Research
Kidney Defects
      polycystic kidney disease

Research Tools
Genetics Research
      Tissue/Cell Markers: kidney specific marker
Tet Expression Systems
      tTA/rtTA Expressing Strains

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(Pax8-rtTA2S*M2)1Koes
Allele Name		transgene insertion 1, Robert Koesters
Allele Type		Transgenic (random, expressed)
Common Name(s)		Pax8-rtTA;
Mutation Made By		Robert Koesters,   Universitaetsklinikum Heidelberg
Strain of Origin		(C57BL/6 x DBA)F2
Expressed Gene		rtTA, reverse tetracycline-controlled transactivator, E. coli
		The tetracycline repressor gene (Tetr), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). One mutant with a four amino acid residue change (rTetR) exhibited dependence on tetracycline for induction of the targeted gene and was used in the rtTA construct (Gossen et al, 1995). rTetr was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16).
Promoter		Pax8, paired box gene 8, mouse, laboratory
Molecular Note		he Pax8-rtTA construct contains an optimized rtTA variant (rtTA2s-M2) cDNA and SV40 polyA sequence replaced at the endogenous ATG translational start site of a murine Pax8 sequence. The rtTA2S*M2 variant contains 5 amino acid changes in the TetR moiety (S12G, E19G, A56P, D148E, and H179R) and a synthetic optimized transactivating domain, resulting in reduced basal activity and enhanced doxycycline sensitivity compared to wild-type rtTA. [MGI Ref ID J:140925]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Pax8-rtTA2S*M2)1Koes, Melt Curve Analysis
Tg(Pax8-rtTA2S*M2)1Koes, QPCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Traykova-Brauch M; Schonig K; Greiner O; Miloud T; Jauch A; Bode M; Felsher DW; Glick AB; Kwiatkowski DJ; Bujard H; Horst J; von Knebel Doeberitz M; Niggli FK; Kriz W; Grone HJ; Koesters R. 2008. An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nat Med 14(9):979-84. [PubMed: 18724376]  [MGI Ref ID J:140925]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, hemizygous mice are bred with wildtype siblings or to C57BL/6J inbred mice.
Mating System	Noncarrier x Hemizygote         (Female x Male)   03-DEC-08
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

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.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Noncarrier
	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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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Ordering and Purchasing Information

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Contact Information
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Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

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

For additional Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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