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| Approximately 85% of the compound mutant females develop focal mammary tumors at 6-10 months of age. Both virgin and breeder mice develop tumors. Approximately 37% of tumor-bearing mice develop metastatic disease to the lung. High expression of neu is detected in tumor tissue while very low levels are found in lung and ovary. Female mice carrying only the neuOT-I/OT-II mutation develop focal mammary tumors at approximately 18 months of age. | |||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
Description
Strain Information
Former Names B6.FVB-Tg(MMTVneu-OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J (Changed: 15-NOV-07 ) Type Congenic; Mutant Strain; Targeted Mutation; Species laboratory mouse Generation N10+ (18-JAN-08) Donating Investigator Brad Nelson, BC Cancer Agency Description
These compound transgenic mice carry a rat Erbb2/HER-2/neu oncogene tagged with ovalbumin epitopes OT-I and OT-II, which are recognized by T cell receptors, under the control of the MMTV promoter (termed fusion protein neuOT-I/OT-II). In addition, this strain carries a mouse Trp53 mini-gene, harboring a G to A point mutation in codon 172 (changing Arg to His; R172H) driven by the rat whey acidic protein promoter.Approximately 85% of compound mutant females develop focal mammary tumors at 6-10 months of age. Both virgin and breeder mice develop tumors. Approximately 37% of tumor-bearing mice develop metastatic disease to the lung. High expression of neu is detected in tumor tissue while very low levels are found in lung and ovary.
Female mice carrying only the neuOT-I/OT-II mutation develop focal mammary tumors at approximately 18 months of age.
This strain may be useful in studies of cancer immunotherapy.
Development
This compound mutant strain carries two independently-created transgenes that were later intercrossed. One construct/line was designed to tag T cell receptor-recognized ovalbumin epitopes SIINFEKL and ISQAVHAAHAEINEAGR with the rat Erbb2/HER-2/neu oncogene, creating a fusion protein under the control of an MMTV promoter (termed neuOT-I/OT-II). The vector was injected into C57BL/6 oocytes. Line C was selected for further studies based on mammary-specific expression and favorable tumor latency and frequency. This line was maintained on a C57BL/6 background. The second transgene contributes the rat whey acidic protein promoter driven mouse Trp53 mini-gene that carries a point mutation in codon 172 (CGC to CAC; Arg172His). This transgenic line was generated by microinjection into FVB mouse embryos and backcrossed to C57BL/6 for more than ten generations by the donating investigator. These independent transgenic strains were interbred to produce this bi-transgenic line.
Related Strains
Strains carrying Tg(Trp53R172H)8512Jmr allele
002659 FVB/N-Tg(Trp53R172H)8512Jmr/J View Strains carrying Tg(Trp53R172H)8512Jmr (1 strain)
004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 002101 B6.129S2-Trp53tm1Tyj/J 007218 B6.129S6-Trp53tm2Xu/J 006980 B6;129-Trp53tm2Xu/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J 002103 B6;129S2-Trp53tm1Tyj/J 002526 C.129S2(B6)-Trp53tm1Tyj/J 002547 C3Ou.129S2(B6)-Trp53tm1Tyj/J 002899 FVB.129S2(B6)-Trp53tm1Tyj/J 002660 FVB/N-Tg(Trp53R172L)4491Jmr/J 003262 STOCK Tg(Trp53A135V)L3Ber/J
002499 C57BL/6J-Tg(WapIGFBP3)67Dlr/J 002660 FVB/N-Tg(Trp53R172L)4491Jmr/J
004997 B6.Cg-Tg(MMTV-TGFBR2)7Hlm/J 002618 B6.Cg-Tg(MMTVtTA)1Mam/J 002375 B6;D2-Tg(MMTVTGFB1)46Hlm/J 002459 B6D2-Tg(MMTVTGFA)254Rjc/J 002373 B6D2-Tg(MMTVTGFA)29Rjc/J 002870 B6SJL-Tg(Wnt1)1Hev/J 005038 FVB-Tg(MMTV-Erbb2)NK1Mul/J 004363 FVB.Cg-Tg(MMTV-vHaras)SH1Led/J 002953 FVB.Cg-Tg(MMTVTGFA)254Rjc/J 002934 FVB.Cg-Tg(Wnt1)1Hev/J 002437 FVB/N-Tg(MMTV-Notch4)3Rnc/J 002374 FVB/N-Tg(MMTV-PyVT)634Mul/J 002376 FVB/N-Tg(MMTVneu)202Mul/J 002933 FVB/NJ-Tg(MMTVTGFB1)46Hlm/J 003690 STOCK Tg(MMTV-Cdc37)1Stp/J 003551 STOCK Tg(MMTV-cre)1Mam/J 003553 STOCK Tg(MMTV-cre)4Mam/J
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
Related Disease (OMIM) Terms
Breast Cancer Mammalian Phenotype Terms assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(MMTV-neu/OT-I/OT-II)CBnel/? Tg(Trp53R172H)8512Jmr/?
involves: C57BL/6 * FVB
- tumorigenesis
- mammary adenocarcinoma (MGI Ref ID J:122846)
- 80% of females develop adencarcinomas by 6-10 months of age; mice generally have 1or two tumors
- tumors are highly mitotic with glandular differentiation in ~30% of cases; ~90% of tumors have minimal necrosis
Research Applications
This mouse can be used to support research in many areas including:
Tcra relatedCancer Research
Increased Tumor Incidence (Mammary Gland Tumors: females only)
Increased Tumor Incidence (Other Tissues/Organs: lung)
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Research Tools
Cancer Research
Tcrb relatedHematological Research
Immunological Defects
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects
Research Tools
Cancer Research (specific T cell deficiency)
Trp53 relatedHematological Research
Immunological Defects
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects
Apoptosis Research
Endogenous Regulators
Cancer Research
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (Other Tissues/Organs: osteosarcoma)
Toxicology
Tumor Suppressor Genes
Immunology and Inflammation Research
Intracellular Signaling Molecules
Mouse/Human Gene Homologs
Li-Fraumeni syndrome
Research Tools
Toxicology Research (B and T cell deficiency) (xenograft transplant host)
Toxicology Research (drug/compound testing)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(MMTV-neu/OT-I/OT-II)CBnel | ||
|---|---|---|---|
| Allele Name | transgene insertion C, Brad Nelson | ||
| Common Name(s) | neuOT-I/OT-II; | ||
| Strain of Origin | C57BL/6 | ||
| Expressed Gene | Tcrb, T-cell receptor beta chain, mouse, laboratory | ||
| Expressed Gene | Tcra, T-cell receptor alpha chain, mouse, laboratory | ||
| Promoter | MMTV, Mouse Mammary Tumor Virus, MMTV | ||
| Molecular Note | The transgene construct was designed to tag T cell receptor-recognized ovalbumin epitopes SIIFEKL (CD8+, OT-1) and ISQAVHAAHAEINEAGR (CD4+, OT-II)with the rat Erbb2/HER-2/neu oncogene under the control of an MMTV promoter creating afusion protein (termed neuOT-I/OT-II). The vector was injected into C57BL/6 oocytes. Line C was selected for further studies based on mammary-specific expression and favorable tumor latency and frequency. [MGI Ref ID J:122846] | ||
| Allele Symbol | Tg(Trp53R172H)8512Jmr | ||
| Allele Name | transgene insertion 8512, Jeffrey Rosen | ||
| Common Name(s) | 172R-H; p53-172H; | ||
| Mutation Made By | Jeffrey Rosen, Baylor College of Medicine | ||
| Strain of Origin | FVB | ||
| Expressed Gene | Trp53, transformation related protein 53, mouse, laboratory | ||
| Promoter | Wap, whey acidic protein, rat | ||
| General Note | On an FVB/N background transgenic mice express TRP53 with both dominant-negative and a gain-of function properties. | ||
| Molecular Note | This transgene contains the rat whey acidic protein promoter and an allele of the mouse Trp53 mini-gene that carries a point mutation in codon 172 (CGC->CAC; Arg172His). [MGI Ref ID J:46426] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(MMTV-neu/OT-I/OT-II)CBnel, SEP PCR, vers. 1
Tg(Trp53R172H)8512Jmr, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Wall EM; Milne K; Martin ML; Watson PH; Theiss P; Nelson BH. 2007. Spontaneous mammary tumors differ widely in their inherent sensitivity to adoptively transferred T cells. Cancer Res 67(13):6442-50. [PubMed: 17616705] [MGI Ref ID J:122846]
Additional References
Tg(Trp53R172H)8512Jmr related
Chatterjee G; Rosner A; Han Y; Zelazny ET; Li B; Cardiff RD; Perkins AS. 2002. Acceleration of Mouse Mammary Tumor Virus-Induced Murine Mammary Tumorigenesis by a p53(172H) Transgene: Influence of FVB Background on Tumor Latency and Identification of Novel Sites of Proviral Insertion. Am J Pathol 161(6):2241-53. [PubMed: 12466138] [MGI Ref ID J:80272]Hadsell DL; Murphy KL; Bonnette SG; Reece N; Laucirica R; Rosen JM. 2000. Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesis. Oncogene 19(7):889-98. [PubMed: 10702797] [MGI Ref ID J:61037]
Li B; Murphy KL; Laucirica R; Kittrell F; Medina D; Rosen JM. 1998. A transgenic mouse model for mammary carcinogenesis. Oncogene 16(8):997-1007. [PubMed: 9519874] [MGI Ref ID J:46426]
Li B; Rosen JM; McMenamin-Balano J; Muller WJ; Perkins AS. 1997. neu/ERBB2 cooperates with p53-172H during mammary tumorigenesis in transgenic mice. Mol Cell Biol 17(6):3155-63. [PubMed: 9154814] [MGI Ref ID J:40336]
Pannellini T; Spadaro M; Di Carlo E; Ambrosino E; Iezzi M; Amici A; Lollini PL; Forni G; Cavallo F; Musiani P. 2006. Timely DNA vaccine combined with systemic IL-12 prevents parotid carcinomas before a dominant-negative p53 makes their growth independent of HER-2/neu expression. J Immunol 176(12):7695-703. [PubMed: 16751417] [MGI Ref ID J:115041]
Zelazny E; Li B; Anagnostopoulos AM; Coleman A; Perkins AS. 2001. Cooperating Oncogenic Events in Murine Mammary Tumorigenesis: Assessment of ErbB2, Mutant p53, and Mouse Mammary Tumor Virus. Exp Mol Pathol 70(3):183-93. [PubMed: 11417997] [MGI Ref ID J:70644]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintained as a live colony hemizygotes (single or double mutant) may be bred. It is not know whether homozygotes are viable and fertile.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date: 01-DEC-08
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
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