Description

Strain Information

Former Names FVB-Tg(MMTV-Erbb2)1Led/J    (Changed: 25-JUL-06 ) Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation F?+N1F11 (31-DEC-07)   Donating Investigator Philip Leder,   Harvard Medical School

Description
These transgenic mice express the activated rat Erbb2 (c-neu) oncogene under the direction of the mouse mammary tumor virus promoter. The activated, or transforming, version of the rat Erbb2 (c-neu) oncogene has a valine to glutamic acid substitution at acid 664, (Val⁶⁶⁴ to Glu⁶⁶⁴). Non-uniform and random transgene expression is detected by RNase protection assay in mammary gland epithelium from hemizygous mice. Tumor formation is multifocal, stochastic and matches the expression pattern of the transgene. While no transgene expression is detected at 5 and 8 weeks of age in normal mammary gland tissue, it is detected in adenocarcinomas from older (23 week old) mice. The donating investigator indicates that 50% of transgenic mice derived from the TG.NK founder line, develop tumors within 6-12 months of age. Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. This mutant mouse strain may be useful in studies of breast cancer.

Development
A transgenic construct containing sequence encoding the mouse mammary tumor virus LTR promoter, 4.6kb of sequence encoding the activated rat Erbb2 (c-neu) oncogene, and SV40 polyadenylation site sequence was microinjected into fertilized FVB/N eggs.

Control Information

	Control
	001800 FVB/NJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Erbb2

002376

FVB/N-Tg(MMTVneu)202Mul/J

View Strains carrying other alleles of Erbb2     (1 strain)

Strains carrying other alleles of MMTV

004997	B6.Cg-Tg(MMTV-TGFBR2)7Hlm/J
002618	B6.Cg-Tg(MMTVtTA)1Mam/J
007962	B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/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
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     (18 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(MMTV-Erbb2)NK1Mul/0

        involves: FVB/N

• tumorigenesis
• mammary adenocarcinoma (MGI Ref ID J:48632)
  • female mice exhibit diffuse, polyclonal tumor masses
  • tumor morphogenesis corresponds to transgene expression
  • tumors are more sparsely distributed than in other lines of the transgene

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tg(MMTV-Erbb2)NK1Mul/Tg(MMTV-Erbb2)NK1Mul

        involves: 129 * C57BL/6 * FVB/N

• tumorigenesis
• mammary adenocarcinoma (MGI Ref ID J:117336)
  • all female virgin mice develop cancer tumors in the breast by 45 weeks of age

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)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(MMTV-Erbb2)NK1Mul
Allele Name		transgene insertion NK1, William Muller
Allele Type		Transgenic (random, expressed)
Common Name(s)		MMTV c-neu; MMTV-erbB2; TG.NK; Tg(MMTV-Erbb2)1Led;
Mutation Made By		Philip Leder,   Harvard Medical School
Strain of Origin		FVB/N
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
General Note		Tumor formation in transgenic mice is multifocal, stochastic, and matches the expression pattern of the transgene. While no transgene expression is detected at 5 and 8 weeks of age in normal mammary gland tissue, expression is detected in adenocarcinomasfrom older (23 week old) mice. 50% of transgenic mice derived from this founder line develop tumors within 6-12 months of age.
Molecular Note		This transgene contains the MMTV (mouse mammary tumor virus) LTR promoter, a 4.6 kb cDNA from the rat Erbb2 (avian erythroblastosis B2) oncogene, and an SV40 polyadenylation site sequence. The activated form of the rat gene is used in this construct, which differs from the wild-type allele by a point mutation, Val664Glu. Non-uniform and random transgene expression is detected by RNase protection assay in mammary gland epithelium from hemizygous transgenic mice. Six transgenic lines were produced (NA, NB,NF, NK, NL and NM). [MGI Ref ID J:48632]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MMTV-Erbb2)NK1Mul, QPCR, vers. 2
Tg(MMTV-Erbb2)NK1Mul, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Muller WJ; Sinn E; Pattengale PK; Wallace R; Leder P. 1988. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54(1):105-15. [PubMed: 2898299]  [MGI Ref ID J:48632]

Additional References

Tg(MMTV-Erbb2)NK1Mul related

Barrington RE; Subler MA; Rands E; Omer CA; Miller PJ; Hundley JE; Koester SK; Troyer DA; Bearss DJ; Conner MW; Gibbs JB; Hamilton K; Koblan KS; Mosser SD; O'Neill TJ; Schaber MD; Senderak ET; Windle JJ; Oliff A; Kohl NE. 1998. A farnesyltransferase inhibitor induces tumor regression in transgenic mice harboring multiple oncogenic mutations by mediating alterations in both cell cycle control and apoptosis. Mol Cell Biol 18(1):85-92. [PubMed: 9418856]  [MGI Ref ID J:78608]

Bentires-Alj M; Neel BG. 2007. Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Cancer Res 67(6):2420-4. [PubMed: 17347513]  [MGI Ref ID J:120339]

Brodie SG; Xu X; Li C; Kuo A; Leder P; Deng CX. 2001. Inactivation of p53 tumor suppressor gene acts synergistically with c-neu oncogene in salivary gland tumorigenesis. Oncogene 20(12):1445-54. [PubMed: 11313888]  [MGI Ref ID J:69223]

Bulavin DV; Phillips C; Nannenga B; Timofeev O; Donehower LA; Anderson CW; Appella E; Fornace AJ Jr. 2004. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Nat Genet 36(4):343-50. [PubMed: 14991053]  [MGI Ref ID J:121570]

Cardiff RD; Anver MR; Gusterson BA; Hennighausen L; Jensen RA; Merino MJ; Rehm S; Russo J; Tavassoli FA; Wakefield LM; Ward JM; Green JE. 2000. The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting [see comments] Oncogene 19(8):968-88. [PubMed: 10713680]  [MGI Ref ID J:61035]

Cardiff RD; Sinn E; Muller W; Leder P. 1991. Transgenic oncogene mice. Tumor phenotype predicts genotype. Am J Pathol 139(3):495-501. [PubMed: 1887859]  [MGI Ref ID J:72086]

Dillon RL; Brown ST; Ling C; Shioda T; Muller WJ. 2007. An EGR2/CITED1 transcription factor complex and the 14-3-3sigma tumor suppressor are involved in regulating ErbB2 expression in a transgenic-mouse model of human breast cancer. Mol Cell Biol 27(24):8648-57. [PubMed: 17938205]  [MGI Ref ID J:128960]

Fantozzi A; Christofori G. 2006. Mouse models of breast cancer metastasis. Breast Cancer Res 8(4):212. [PubMed: 16887003]  [MGI Ref ID J:116013]

Ju X; Katiyar S; Wang C; Liu M; Jiao X; Li S; Zhou J; Turner J; Lisanti MP; Russell RG; Mueller SC; Ojeifo J; Chen WS; Hay N; Pestell RG. 2007. Akt1 governs breast cancer progression in vivo. Proc Natl Acad Sci U S A 104(18):7438-43. [PubMed: 17460049]  [MGI Ref ID J:121297]

Koyama H; Kobayashi N; Harada M; Takeoka M; Kawai Y; Sano K; Fujimori M; Amano J; Ohhashi T; Kannagi R; Kimata K; Taniguchi S; Itano N. 2008. Significance of tumor-associated stroma in promotion of intratumoral lymphangiogenesis: pivotal role of a hyaluronan-rich tumor microenvironment. Am J Pathol 172(1):179-93. [PubMed: 18079437]  [MGI Ref ID J:130531]

Landis MW; Pawlyk BS; Li T; Sicinski P; Hinds PW. 2006. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell 9(1):13-22. [PubMed: 16413468]  [MGI Ref ID J:105045]

Law M; Forrester E; Chytil A; Corsino P; Green G; Davis B; Rowe T; Law B. 2006. Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these complexes. Cancer Res 66(2):1070-80. [PubMed: 16424043]  [MGI Ref ID J:106547]

Li Y; Zhang Y; Hill J; Kim HT; Shen Q; Bissonnette RP; Lamph WW; Brown PH. 2008. The rexinoid, bexarotene, prevents the development of premalignant lesions in MMTV-erbB2 mice. Br J Cancer 98(8):1380-8. [PubMed: 18362934]  [MGI Ref ID J:137272]

Li Y; Zhang Y; Hill J; Shen Q; Kim HT; Xu X; Hilsenbeck SG; Bissonnette RP; Lamph WW; Brown PH. 2007. The Rexinoid LG100268 prevents the development of preinvasive and invasive estrogen receptor negative tumors in MMTV-erbB2 mice. Clin Cancer Res 13(20):6224-31. [PubMed: 17947490]  [MGI Ref ID J:131196]

Luijten M; Thomsen AR; van den Berg JA; Wester PW; Verhoef A; Nagelkerke NJ; Adlercreutz H; van Kranen HJ; Piersma AH; Sorensen IK; Rao GN; van Kreijl CF. 2004. Effects of soy-derived isoflavones and a high-fat diet on spontaneous mammary tumor development in Tg.NK (MMTV/c-neu) mice. Nutr Cancer 50(1):46-54. [PubMed: 15572297]  [MGI Ref ID J:95478]

Luijten M; Verhoef A; Dormans JA; Beems RB; Cremers HW; Nagelkerke NJ; Adlercreutz H; Penalvo JL; Piersma AH. 2007. Modulation of mammary tumor development in Tg.NK (MMTV/c-neu) mice by dietary fatty acids and life stage-specific exposure to phytoestrogens. Reprod Toxicol 23(3):407-13. [PubMed: 17229545]  [MGI Ref ID J:121510]

Maroulakou IG; Oemler W; Naber SP; Tsichlis PN. 2007. Akt1 ablation inhibits, whereas Akt2 ablation accelerates, the development of mammary adenocarcinomas in mouse mammary tumor virus (MMTV)-ErbB2/neu and MMTV-polyoma middle T transgenic mice. Cancer Res 67(1):167-77. [PubMed: 17210696]  [MGI Ref ID J:117336]

Mortensen A; Kramer F; Lindecrona RH; Sorensen IK. 2004. Investigation of the effect of lignans on murine mammary gland differentiation in TG.NK mice. Asia Pac J Clin Nutr 13(Suppl):S172. [PubMed: 15294749]  [MGI Ref ID J:92112]

Rajkumar L; Kittrell FS; Guzman RC; Brown PH; Nandi S; Medina D. 2007. Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models. Breast Cancer Res 9(1):R12. [PubMed: 17257424]  [MGI Ref ID J:121486]

Rao GN; Ney E; Herbert RA. 1999. Changes associated with delay of mammary cancer by retinoid analogues in transgenic mice bearing c-neu oncogene Breast Cancer Res Treat 58(3):241-54. [PubMed: 10718486]  [MGI Ref ID J:61198]

Rao GN; Ney E; Herbert RA. 2000. Effect of melatonin and linolenic acid on mammary cancer in transgenic mice with c-neu breast cancer oncogene. Breast Cancer Res Treat 64(3):287-96. [PubMed: 11200779]  [MGI Ref ID J:67457]

Rao GN; Ney E; Herbert RA. 1997. Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue. Breast Cancer Res Treat 45(2):149-58. [PubMed: 9342440]  [MGI Ref ID J:43631]

Ray D; Terao Y; Fuhrken PG; Ma ZQ; DeMayo FJ; Christov K; Heerema NA; Franks R; Tsai SY; Papoutsakis ET; Kiyokawa H. 2007. Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability. Cancer Res 67(3):984-91. [PubMed: 17283130]  [MGI Ref ID J:118218]

Ray D; Terao Y; Nimbalkar D; Hirai H; Osmundson EC; Zou X; Franks R; Christov K; Kiyokawa H. 2007. Hemizygous disruption of Cdc25A inhibits cellular transformation and mammary tumorigenesis in mice. Cancer Res 67(14):6605-11. [PubMed: 17638870]  [MGI Ref ID J:123144]

Shen Q; Brown PH. 2005. Transgenic mouse models for the prevention of breast cancer. Mutat Res 576(1-2):93-110. [PubMed: 15888345]  [MGI Ref ID J:100623]

Taverna D; Crowley D; Connolly M; Bronson RT; Hynes RO. 2005. A direct test of potential roles for beta3 and beta5 integrins in growth and metastasis of murine mammary carcinomas. Cancer Res 65(22):10324-9. [PubMed: 16288021]  [MGI Ref ID J:103405]

Thomsen AR; Mortensen A; Breinholt VM; Lindecrona RH; Penalvo JL; Sorensen IK. 2005. Influence of Prevastein, an isoflavone-rich soy product, on mammary gland development and tumorigenesis in Tg.NK (MMTV/c-neu) mice. Nutr Cancer 52(2):176-88. [PubMed: 16201849]  [MGI Ref ID J:104183]

Tilli MT; Furth PA. 2003. Conditional mouse models demonstrate oncogene-dependent differences in tumor maintenance and recurrence. Breast Cancer Res 5(4):202-5. [PubMed: 12817992]  [MGI Ref ID J:84503]

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]

Yu Q; Sicinska E; Geng Y; Ahnstrom M; Zagozdzon A; Kong Y; Gardner H; Kiyokawa H; Harris LN; Stal O; Sicinski P. 2006. Requirement for CDK4 kinase function in breast cancer. Cancer Cell 9(1):23-32. [PubMed: 16413469]  [MGI Ref ID J:105043]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	The resulting transgenic mice were bred to homozygosity, and the genotypes confirmed by quantitative PCR.
Mating System	Homozygote x Homozygote         (Female x Male)
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 ~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 48 hours of 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
	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.

General Terms and Conditions

See Terms of Use

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

OncoMouse^® requires a license from DuPont, see Licenses for Strains with OncoMouse^® Technology.

Contact information

General inquiries

Contracts Administration

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.