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; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System See Colony Maintenance under the Health & husbandry tab         (Female x Male)   01-MAY-09 Species laboratory mouse Generation N10+N10 (17-AUG-12) Generation Definitions   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 neu^OT-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 neu^OT-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 neu^OT-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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(Trp53R172H)8512Jmr allele

002659

FVB/N-Tg(Trp53R172H)8512Jmr/J

View Strains carrying   Tg(Trp53R172H)8512Jmr     (1 strain)

Strains carrying other alleles of Erbb2

010577	B6;SJL-Tg(tetO-Erbb2*)8-4Jek/J
005038	FVB-Tg(MMTV-Erbb2)NK1Mul/J
002376	FVB/N-Tg(MMTVneu)202Mul/J

View Strains carrying other alleles of Erbb2     (3 strains)

Strains carrying other alleles of Trp53

004301	129-Trp53tm1Holl/J
002080	129-Trp53tm1Tyj/J
008652	129S-Trp53tm2Tyj/J
008651	129S-Trp53tm3Tyj/J
008462	B6.129P2-Trp53tm1Brn/J
002101	B6.129S2-Trp53tm1Tyj/J
008183	B6.129S4(Cg)-Trp53tm2.1Tyj/J
008182	B6.129S4-Trp53tm3.1Tyj/J
007218	B6.129S6-Trp53tm2Xu/J
011109	B6.Cg-Trp53tm2Glo/Kvm
017767	B6;129-Trp53tm1.1Dgk/J
008045	B6;129-Trp53tm2Holl/J
006980	B6;129-Trp53tm2Xu/J
008191	B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J
002103	B6;129S2-Trp53tm1Tyj/J
008181	B6;129S4-Trp53tm4Tyj/J
008361	B6;129S4-Trp53tm5Tyj/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
017530	STOCK Iis2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J
012620	STOCK Trp53tm1Brd Brca1tm1Aash Tg(LGB-cre)74Acl/J
003262	STOCK Tg(Trp53A135V)L3Ber/J

View Strains carrying other alleles of Trp53     (24 strains)

Strains carrying other alleles of Wap

002499	C57BL/6J-Tg(WapIGFBP3)67Dlr/J
002677	FVB.Cg-Tg(WapMyc)212Bri/J
002660	FVB/N-Tg(Trp53R172L)4491Jmr/J

View Strains carrying other alleles of Wap     (3 strains)

Strains carrying other alleles of MMTV

004997	B6.Cg-Tg(MMTV-TGFBR2)7Hlm/J
002618	B6.Cg-Tg(MMTVtTA)1Mam/J
002375	B6;D2-Tg(MMTVTGFB1)46Hlm/J
010576	B6;SJL-Tg(MMTV-rtTA)4-1Jek/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
003337	STOCK Tg(MMTV-PIP)1Shu/J
003551	STOCK Tg(MMTV-cre)1Mam/J
003553	STOCK Tg(MMTV-cre)4Mam/J

View Strains carrying other alleles of MMTV     (19 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Breast Cancer

- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Adrenocortical Carcinoma, Hereditary; ADCC   (TP53) Basal Cell Carcinoma, Susceptibility to, 7; BCC7   (TP53) Colorectal Cancer; CRC   (TP53) Glioma Susceptibility 1; GLM1   (TP53) Hepatocellular Carcinoma   (TP53) Li-Fraumeni Syndrome 1; LFS1   (TP53) Nasopharyngeal Carcinoma   (TP53) Osteogenic Sarcoma   (TP53) Pancreatic Cancer   (TP53) Papilloma of Choroid Plexus   (TP53)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      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
  • 80% of females develop adencarcinomas by 6-10 months of age; mice generally have 1or two tumors   (MGI Ref ID J:122846)
  • tumors are highly mitotic with glandular differentiation in ~30% of cases; ~90% of tumors have minimal necrosis   (MGI Ref ID J:122846)

View Research Applications

Research Applications

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

Cancer Research
Increased Tumor Incidence
      Mammary Gland Tumors
      Mammary Gland Tumors: females only
      Other Tissues/Organs
      Other Tissues/Organs: lung

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Research Tools
Cancer Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(MMTV-neu/OT-I/OT-II)CBnel
Allele Name		transgene insertion C, Brad Nelson
Allele Type		Transgenic (random, expressed)
Common Name(s)		MMTV-HER2/Neu-Ovalbumin; neuOT-I/OT-II;
Strain of Origin		C57BL/6
Expressed Gene		Erbb2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), rat
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
Allele Type		Transgenic (random, expressed)
Common Name(s)		172R-H; Wap-p53R172H; p53(R172H); p53-172H;
Mutation Made By		Dr. 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(Trp53R172H)8512Jmr-alternate1, Separated PCR
Tg(MMTV-neu/OT-I/OT-II)CBnel, Standard PCR
Tg(Trp53R172H)8512Jmr, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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(MMTV-neu/OT-I/OT-II)CBnel related

Ho VW; Leung K; Hsu A; Luk B; Lai J; Shen SY; Minchinton AI; Waterhouse D; Bally MB; Lin W; Nelson BH; Sly LM; Krystal G. 2011. A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation. Cancer Res 71(13):4484-93. [PubMed: 21673053]  [MGI Ref ID J:173599]

Pere H; Montier Y; Bayry J; Quintin-Colonna F; Merillon N; Dransart E; Badoual C; Gey A; Ravel P; Marcheteau E; Batteux F; Sandoval F; Adotevi O; Chiu C; Garcia S; Tanchot C; Lone YC; Ferreira LC; Nelson BH; Hanahan D; Fridman WH; Johannes L; Tartour E. 2011. A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens. Blood 118(18):4853-62. [PubMed: 21908423]  [MGI Ref ID J:178793]

Tg(Trp53R172H)8512Jmr related

Blanco-Aparicio C; Canamero M; Cecilia Y; Pequeno B; Renner O; Ferrer I; Carnero A. 2010. Exploring the gain of function contribution of AKT to mammary tumorigenesis in mouse models. PLoS One 5(2):e9305. [PubMed: 20174572]  [MGI Ref ID J:157988]

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]

Francis SM; Chakrabarti S; Dick FA. 2011. A context-specific role for retinoblastoma protein-dependent negative growth control in suppressing mammary tumorigenesis. PLoS One 6(2):e16434. [PubMed: 21364977]  [MGI Ref ID J:171066]

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]

Kim IS; Baek SH. 2010. Mouse models for breast cancer metastasis. Biochem Biophys Res Commun 394(3):443-7. [PubMed: 20230796]  [MGI Ref ID J:159230]

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]

Pere H; Montier Y; Bayry J; Quintin-Colonna F; Merillon N; Dransart E; Badoual C; Gey A; Ravel P; Marcheteau E; Batteux F; Sandoval F; Adotevi O; Chiu C; Garcia S; Tanchot C; Lone YC; Ferreira LC; Nelson BH; Hanahan D; Fridman WH; Johannes L; Tartour E. 2011. A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens. Blood 118(18):4853-62. [PubMed: 21908423]  [MGI Ref ID J:178793]

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

Animal Health Reports

Room Number           FGB29

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.
Mating System	See Colony Maintenance under the Health & husbandry tab         (Female x Male)   01-MAY-09
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

 

This strain is currently On Hold.

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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.

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