Strain Name:

B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J

Stock Number:

007962

Availability:

Under Development for Distribution Colony

Use Restrictions Apply, see Purchasing Information
To register your interest in this strain go to the Strain Interest Form.
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

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;
Specieslaboratory mouse
GenerationN10+ (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)

Strains carrying other alleles of Tcra
005308   B10.Cg-H2d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005895   B10.Cg-Thy1a H2d Tg(TcraCl1,TcrbCl1)1Shrm/J
002761   B10.Cg-Tg(TcrAND)53Hed/J
003147   B10.D2-Hc1 H2d H2-T18c/nSnJ-Tg(DO11.10)10Dlo/J
003199   B10.PL-H2u H2-T18a/(73NS)Sn-Tg(TCRA)B1Jg/J
002116   B6.129S2-Tcratm1Mom/J
005023   B6.Cg-Thy1a/Cy Tg(TcraTcrb)8Rest/J
005655   B6.Cg-Tg(Tcra,Tcrb)3Ayr/J
008006   B6.Cg-Tg(Tcra51-11.5,Tcrb51-11.5)AR206Ayr/J
005236   B6.Cg-Tg(TcraY1,TcrbY1)416Tev/J
002115   B6;129S2-Tcratm1Mom/J
004694   B6;D2-Tg(TcrLCMV)327Sdz/JDvsJ
002408   B6;SJL-Tg(TcrAND)53Hed/J
004364   C.Cg-Tcratm1Mom Tcrbtm1Mom/J
003303   C.Cg-Tg(DO11.10)10Dlo/J
006912   C57BL/6-Tg(Tcra2D2,Tcrb2D2)1Kuch/J
003831   C57BL/6-Tg(TcraTcrb)1100Mjb/J
004194   C57BL/6-Tg(TcraTcrb)425Cbn/J
005307   CBy.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005922   CBy.Cg-Thy1a Tg(TcraCl1,TcrbCl1)1Shrm/J
007080   CByJ.B6-Tg(TcraTcrb)1100Mjb/J
005694   D1Lac.Cg-Tg(Tcra,Tcrb)24Efro/J
004444   NOD.129P2(C)-Tcratm1Mjo/DoiJ
006436   NOD.Cg-(Gpi1-D7Mit346)C57BL/6J Tg(TcraAI4)1Dvs/DvsJ
004257   NOD.Cg-Prkdcscid Tg(TcrLCMV)327Sdz/Dvs
004259   NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
004347   NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs/DvsJ
005686   NOD.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
004696   NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ
004460   NOD.Cg-Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi/DoiJ
005868   NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ
006303   NOD.FVB-Tg(TcraBDC12-4.1)10Jos/GseJ
004334   NOD/ShiLt-Tg(TcraAI4)1Dvs
003868   NOD/ShiLt-Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
002597   STOCK Tg(TcrHEL3A9)1Mmd/J
View Strains carrying other alleles of Tcra     (35 strains)

Strains carrying other alleles of Tcrb
005308   B10.Cg-H2d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005895   B10.Cg-Thy1a H2d Tg(TcraCl1,TcrbCl1)1Shrm/J
002761   B10.Cg-Tg(TcrAND)53Hed/J
003147   B10.D2-Hc1 H2d H2-T18c/nSnJ-Tg(DO11.10)10Dlo/J
003200   B10.PL-H2u H2-T18a/(73NS)Sn-Tg(TCRB)C14Jg/J
002122   B6.129P2-Tcrbtm1Mom Tcrdtm1Mom/J
002118   B6.129P2-Tcrbtm1Mom/J
005023   B6.Cg-Thy1a/Cy Tg(TcraTcrb)8Rest/J
005655   B6.Cg-Tg(Tcra,Tcrb)3Ayr/J
008006   B6.Cg-Tg(Tcra51-11.5,Tcrb51-11.5)AR206Ayr/J
005236   B6.Cg-Tg(TcraY1,TcrbY1)416Tev/J
002121   B6;129P-Tcrbtm1Mom Tcrdtm1Mom/J
002117   B6;129P2-Tcrbtm1Mom/J
004694   B6;D2-Tg(TcrLCMV)327Sdz/JDvsJ
002408   B6;SJL-Tg(TcrAND)53Hed/J
004364   C.Cg-Tcratm1Mom Tcrbtm1Mom/J
003303   C.Cg-Tg(DO11.10)10Dlo/J
006912   C57BL/6-Tg(Tcra2D2,Tcrb2D2)1Kuch/J
003831   C57BL/6-Tg(TcraTcrb)1100Mjb/J
004194   C57BL/6-Tg(TcraTcrb)425Cbn/J
005307   CBy.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
005922   CBy.Cg-Thy1a Tg(TcraCl1,TcrbCl1)1Shrm/J
007080   CByJ.B6-Tg(TcraTcrb)1100Mjb/J
005694   D1Lac.Cg-Tg(Tcra,Tcrb)24Efro/J
006437   NOD.Cg-(Gpi1-D7Mit346)C57BL/6J Tg(TcrbAI4)1Dvs/DvsJ
004257   NOD.Cg-Prkdcscid Tg(TcrLCMV)327Sdz/Dvs
004259   NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
004348   NOD.Cg-Rag1tm1Mom Tg(TcrbAI4)1Dvs/DvsJ
005686   NOD.Cg-Thy1a Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
004696   NOD.Cg-Tg(TcrLCMV)327Sdz/DvsJ
004460   NOD.Cg-Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi/DoiJ
005868   NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa/DvsJ
006304   NOD.FVB-Tg(TcrbBDC12-4.1)82Gse/GseJ
003868   NOD/ShiLt-Tg(TcraAI4)1Dvs/+ Tg(TcrbAI4)1Dvs/+
004335   NOD/ShiLt-Tg(TcrbAI4)1Dvs
002597   STOCK Tg(TcrHEL3A9)1Mmd/J
View Strains carrying other alleles of Tcrb     (36 strains)

View Strains carrying other alleles of Trp53     (12 strains)

Strains carrying other alleles of Wap
002499   C57BL/6J-Tg(WapIGFBP3)67Dlr/J
002660   FVB/N-Tg(Trp53R172L)4491Jmr/J
View Strains carrying other alleles of Wap     (2 strains)

View Strains carrying other alleles of MMTV     (17 strains)

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:

Cancer 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

Tcra related

Hematological 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)

Tcrb related

Hematological Research
Immunological Defects

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency
Inflammation
T Cell Receptor Signaling Defects

Trp53 related

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 OriginC57BL/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 OriginFVB
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 & HusbandryWhen 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.

View All Strains Under Development

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