Former Names FVB-Tg(MMTV-Erbb2)1Led/J (Changed: 25-JUL-06 ) Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Species laboratory mouse Generation F?+N1F13 (31-DEC-08)
Generation DefinitionsDonating Investigator Dr. 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.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 | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Erbb2
007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 010577 B6;SJL-Tg(tetO-Erbb2*)8-4Jek/J 002376 FVB/N-Tg(MMTVneu)202Mul/J View Strains carrying other alleles of Erbb2 (3 strains)
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 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 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)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Tg(MMTV-Erbb2)NK1Mul/0
involves: FVB/N
- tumorigenesis
- mammary adenocarcinoma
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(MMTV-Erbb2)NK1Mul/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N
- tumorigenesis
- increased mammary gland tumor incidence (MGI Ref ID J:76653)
- increased tumor latency
- mice display 50% tumor incidence at 52 weeks of age compared to 25 weeks of age in mice on an FVB/N background (MGI Ref ID J:76653)
- mice ovariectomized at 18-20 days of age, but not those ovariectomized at 16-20 weeks of age, display a further delay in tumor onset (50% incidence at 62 weeks of age) (MGI Ref ID J:76653)
- breeding females accelerates tumor development (50% incidence at 32 weeks of age) (MGI Ref ID J:76653)
- reproductive system phenotype
- *normal* reproductive system phenotype
- unlike in previous reports, mammary gland ductal structure is not different from controls prior to the onset of tumor formation (MGI Ref ID J:76653)
Tg(MMTV-Erbb2)NK1Mul/Tg(MMTV-Erbb2)NK1Mul
involves: 129 * C57BL/6 * FVB/N
- tumorigenesis
- mammary adenocarcinoma
- all female virgin mice develop cancer tumors in the breast by 45 weeks of age (MGI Ref ID J:117336)
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
| Allele Symbol | Tg(MMTV-Erbb2)NK1Mul | ||
|---|---|---|---|
| Allele Name | transgene insertion NK1, William Muller | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | HER-2/neu; MMTV c-neu; MMTV-Tg.NK; MMTV-erbB2; MMTV-neu; TG.NK; Tg(MMTV-Erbb2)1Led; | ||
| Mutation Made By | Dr. 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 Protocols
Tg(MMTV-Erbb2)NK1Mul, QPCR
Tg(MMTV-Erbb2)NK1Mul, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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]
Tg(MMTV-Erbb2)NK1Mul relatedBai L; Rohrschneider LR. 2010. s-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue. Genes Dev 24(17):1882-92. [PubMed: 20810647] [MGI Ref ID J:163521]
Balboni AL; Hutchinson JA; DeCastro AJ; Cherukuri P; Liby K; Sporn MB; Schwartz GN; Wells WA; Sempere LF; Yu PB; DiRenzo J. 2013. DeltaNp63alpha-mediated activation of bone morphogenetic protein signaling governs stem cell activity and plasticity in normal and malignant mammary epithelial cells. Cancer Res 73(2):1020-30. [PubMed: 23243027] [MGI Ref ID J:194364]
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]
Bienvenu F; Jirawatnotai S; Elias JE; Meyer CA; Mizeracka K; Marson A; Frampton GM; Cole MF; Odom DT; Odajima J; Geng Y; Zagozdzon A; Jecrois M; Young RA; Liu XS; Cepko CL; Gygi SP; Sicinski P. 2010. Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature 463(7279):374-8. [PubMed: 20090754] [MGI Ref ID J:156591]
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]
Brown NE; Jeselsohn R; Bihani T; Hu MG; Foltopoulou P; Kuperwasser C; Hinds PW. 2012. Cyclin D1 activity regulates autophagy and senescence in the mammary epithelium. Cancer Res 72(24):6477-89. [PubMed: 23041550] [MGI Ref ID J:193650]
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]
Cameron HL; Foster WG. 2009. Developmental and lactational exposure to dieldrin alters mammary tumorigenesis in Her2/neu transgenic mice. PLoS ONE 4(1):e4303. [PubMed: 19173004] [MGI Ref ID J:144833]
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]
Chen DY; Lee Y; Van Tine BA; Searleman AC; Westergard TD; Liu H; Tu HC; Takeda S; Dong Y; Piwnica-Worms DR; Oh KJ; Korsmeyer SJ; Hermone A; Gussio R; Shoemaker RH; Cheng EH; Hsieh JJ. 2012. A pharmacologic inhibitor of the protease Taspase1 effectively inhibits breast and brain tumor growth. Cancer Res 72(3):736-46. [PubMed: 22166309] [MGI Ref ID J:181107]
Choi YJ; Li X; Hydbring P; Sanda T; Stefano J; Christie AL; Signoretti S; Look AT; Kung AL; von Boehmer H; Sicinski P. 2012. The requirement for cyclin D function in tumor maintenance. Cancer Cell 22(4):438-51. [PubMed: 23079655] [MGI Ref ID J:192032]
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]
Gabai VL; Meng L; Kim G; Mills TA; Benjamin IJ; Sherman MY. 2012. Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR. Mol Cell Biol 32(5):929-40. [PubMed: 22215620] [MGI Ref ID J:183719]
Hewitt SC; Bocchinfuso WP; Zhai J; Harrell C; Koonce L; Clark J; Myers P; Korach KS. 2002. Lack of ductal development in the absence of functional estrogen receptor alpha delays mammary tumor formation induced by transgenic expression of ErbB2/neu. Cancer Res 62(10):2798-805. [PubMed: 12019156] [MGI Ref ID J:76653]
Jeselsohn R; Brown NE; Arendt L; Klebba I; Hu MG; Kuperwasser C; Hinds PW. 2010. Cyclin D1 Kinase Activity Is Required for the Self-Renewal of Mammary Stem and Progenitor Cells that Are Targets of MMTV-ErbB2 Tumorigenesis. Cancer Cell 17(1):65-76. [PubMed: 20129248] [MGI Ref ID J:156929]
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]
Lehembre F; Yilmaz M; Wicki A; Schomber T; Strittmatter K; Ziegler D; Kren A; Went P; Derksen PW; Berns A; Jonkers J; Christofori G. 2008. NCAM-induced focal adhesion assembly: a functional switch upon loss of E-cadherin. EMBO J 27(19):2603-15. [PubMed: 18772882] [MGI Ref ID J:141157]
Leng X; Ding T; Lin H; Wang Y; Hu L; Hu J; Feig B; Zhang W; Pusztai L; Symmans WF; Wu Y; Arlinghaus RB. 2009. Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis. Cancer Res 69(22):8579-84. [PubMed: 19887608] [MGI Ref ID J:154442]
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]
Meyer DS; Brinkhaus H; Muller U; Muller M; Cardiff RD; Bentires-Alj M. 2011. Luminal Expression of PIK3CA Mutant H1047R in the Mammary Gland Induces Heterogeneous Tumors. Cancer Res 71(13):4344-51. [PubMed: 21482677] [MGI Ref ID J:173655]
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]
Pradeep CR; Kostler WJ; Lauriola M; Granit RZ; Zhang F; Jacob-Hirsch J; Rechavi G; Nair HB; Hennessy BT; Gonzalez-Angulo AM; Tekmal RR; Ben-Porath I; Mills GB; Domany E; Yarden Y. 2012. Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling. Oncogene 31(7):907-17. [PubMed: 21743488] [MGI Ref ID J:181067]
Quan L; Dittmar A; Zhou Y; Hutson A; Stassen AP; Demant P. 2012. Susceptibility loci affecting ERBB2/neu-induced mammary tumorigenesis in mice. Genes Chromosomes Cancer 51(7):631-43. [PubMed: 22419448] [MGI Ref ID J:185943]
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]
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Roberts PJ; Bisi JE; Strum JC; Combest AJ; Darr DB; Usary JE; Zamboni WC; Wong KK; Perou CM; Sharpless NE. 2012. Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. J Natl Cancer Inst 104(6):476-87. [PubMed: 22302033] [MGI Ref ID J:184943]
Schulz R; Marchenko ND; Holembowski L; Fingerle-Rowson G; Pesic M; Zender L; Dobbelstein M; Moll UM. 2012. Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression. J Exp Med 209(2):275-89. [PubMed: 22271573] [MGI Ref ID J:181875]
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Strumane K; Rygiel T; van der Valk M; Collard JG. 2009. Tiam1-deficiency impairs mammary tumor formation in MMTV-c-neu but not in MMTV-c-myc mice. J Cancer Res Clin Oncol 135(1):69-80. [PubMed: 18592271] [MGI Ref ID J:142164]
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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]
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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) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $177.00 Female or Male Homozygous for Tg(MMTV-Erbb2)NK1Mul
Price per Pair (US dollars $) Pair Genotype $354.00 Homozygous for Tg(MMTV-Erbb2)NK1Mul x Homozygous for Tg(MMTV-Erbb2)NK1Mul Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
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Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $230.10 Female or Male Homozygous for Tg(MMTV-Erbb2)NK1Mul
Price per Pair (US dollars $) Pair Genotype $460.20 Homozygous for Tg(MMTV-Erbb2)NK1Mul x Homozygous for Tg(MMTV-Erbb2)NK1Mul Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
For Licensing and Use Restrictions view the link(s) below:
- Notice to customers in Canada.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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