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| These TRE-MET transgenic mice express human MET (met proto-oncogene (hepatocyte growth factor receptor)) gene under the control of a tetracycline-responsive promoter element (TRE or tetO). When bred with another transgenic mouse expressing reverse tetracycline-controlled transactivator protein or tetracycline-controlled transactivator protein, a bitransgenic animal can be produced that has tissue-specific expression of MET that can be regulated with the tetracycline analog, doxycycline. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
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- Health & husbandry
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Description
Strain Information
Type Coisogenic; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 24-FEB-09 Species laboratory mouse Generation F?+ (23-FEB-09) Donating Investigator Rong Wang, Univ of California Medical Center (UCSF) Description
These transgenic mice express the human MET (met proto-oncogene (hepatocyte growth factor receptor)) gene under the control of a tetracycline-responsive promoter element (TRE or tetO). When bred with another transgenic mouse expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), a bitransgenic animal can be produced that has tissue-specific expression of MET that can be regulated with the tetracycline analog, doxycycline. When bred to mice carrying the transgene LAP-tTA, (see Stock No. 003563 for example), the resulting bi-transgenic mice have inducible overexpression of MET in hepatocytes and represent an effective tool for studying hepatocellular carcinoma.Development
The TRE-MET transgene was designed with the human MET (met proto-oncogene (hepatocyte growth factor receptor)) coding sequence, under the control of heptamerized tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) sequences and a cytomegalovirus (hCMV) minimal promoter with a beta-globin poly A signal. This transgene was injected into fertilized FVB/N mouse oocytes. Founder line 23 was subsequently established.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of MET
002675 FVB/N-Tg(MtTPRMET)243Lng/J 002775 FVB/N-Tg(MtTPRMET)773Lng/J View Strains carrying other alleles of MET (2 strains)
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(tetO-MET)23Rwng/0 Tg(tTALap)5Bjd/0
involves: FVB/N * NMRI
- life span-post-weaning/aging
- premature death (MGI Ref ID J:69731)
- mice from 2 lines (1 and 2) of double transgenic founders die within 2 months postpartum; early mortality can be prevented by repression of MET expression with doxycycline administration to mating parents, and then to pups until 4 weeks of age
- with this doxycycline treatment, animals appear normal until 10 months of age, then mice start dying
- mice from 2 other lines (3 and 4) of double transgenic parents are healthy at birth, then begin to die at 4 months of age
- growth/size phenotype
- cachexia (MGI Ref ID J:69731)
- animals dying without evidence of tumors are usually cachexic
- liver/biliary system phenotype
- abnormal hepatocyte morphology (MGI Ref ID J:69731)
- hepatocytes in foci of hyperplasia develop foamy cytoplasm containing fat deposits
- with progression of hyperplastic foci toward malignancy, cytologic changes are observed such as cellular and nuclear enlargement with disorganization of cell plate and lobular structures; malignant foci enlarge and develop trabeculae lined with endothelial cells, often separated from each other by blood-filled spaces
- enlarged liver (MGI Ref ID J:69731)
- pups are born with enlarged and fatty livers
- focal hepatic necrosis (MGI Ref ID J:69731)
- fully developed tumors often display areas of necrosis
- hepatic steatosis (MGI Ref ID J:69731)
- pups are born with enlarged and fatty livers
- jaundice (MGI Ref ID J:69731)
- animals dying without evidence of tumors display jaundice
- tumorigenesis
- hepatocellular carcinoma (MGI Ref ID J:69731)
- 85% of animals dying after 10 months after receiving DOX till 4 weeks of age show hepatocellular carcinoma (HCC); incidence by 1 year is >60% in lines 1 and 2
- for lines 3 and 4, 85% of deaths are accompanied by HCC, which appears as an abdominal mass at 6 months of age or later; incidence by 1 year is 60%
- by 60 weeks of age, many small foci of hyperplasia are detected, often around central hepatic lobule and become more numerous, larger, and uniformly distributed by 4 months of age
- zones of progression to malignancy are observed within hyperplasias by 6 months, with cells in the zones showing poor organization and less differentiation than normal livers
- majority of moribund mice treated with doxycycline regain health tumors nearly regress completely, with liver morphology becoming almost normal by 4 months of treatment
- fully developed tumors often display areas of necrosis
This mouse can be used to support research in many areas including:
MET relatedResearch Tools
Cancer Research
Tetop Tet System
Tet Expression Systems
tTA/rtTA Responsive Strains
Cancer Research
Increased Tumor Incidence
Mammary Gland Tumors
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(tetO-MET)23Rwng | ||
|---|---|---|---|
| Allele Name | transgene insertion 23, Rong Wang | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | TRE-MET; TRE-hMET; | ||
| Mutation Made By | Christin Munkittrick, | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | MET, met proto-oncogene (hepatocyte growth factor receptor), human | ||
| Promoter | tetO, tet operator, | ||
| Molecular Note | The TRE-MET transgene was designed with the human MET (met proto-oncogene (hepatocyte growth factor receptor)) coding sequence, under the control of heptamerized tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) sequences and a cytomegalovirus (hCMV) minimal promoter with a beta-globin poly A signal. Founder line 23 was subsequently established. [MGI Ref ID J:69731] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(tetO-MET)23Rwng, Standard PCR
Tg(tetO-MET), Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Wang R; Ferrell LD; Faouzi S; Maher JJ; Bishop JM. 2001. Activation of the met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice. J Cell Biol 153(5):1023-34. [PubMed: 11381087] [MGI Ref ID J:69731]
Additional References
Tg(tetO-MET)23Rwng relatedTward AD; Jones KD; Yant S; Cheung ST; Fan ST; Chen X; Kay MA; Wang R; Bishop JM. 2007. Distinct pathways of genomic progression to benign and malignant tumors of the liver. Proc Natl Acad Sci U S A 104(37):14771-14776. [PubMed: 17785413] [MGI Ref ID J:124960]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number MGL375/MGL377
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these founder line 23 mice may be bred as homozygotes. Mating System Noncarrier x Hemizygote (Female x Male) 24-FEB-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 $243.50 Female or Male Hemizygous for Tg(tetO-MET)23Rwng
Pairs /Price (US dollars $) Pair Genotype $297.85 Hemizygous for Tg(tetO-MET)23Rwng x Noncarrier $297.85 Noncarrier x Hemizygous for Tg(tetO-MET)23Rwng
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Hemizygous for Tg(tetO-MET)23Rwng
Pairs /Price (US dollars $) Pair Genotype $387.30 Hemizygous for Tg(tetO-MET)23Rwng x Noncarrier $387.30 Noncarrier x Hemizygous for Tg(tetO-MET)23Rwng
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 | ||
|---|---|---|
| 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. | ||
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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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