Description

Strain Information

Former Names B6;129S4-Ptentm1Hwu    (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N?+1F8 (23-JUL-08)   Donating Investigator Hong Wu,   UCLA

Description
These mice possess loxP sites on either side of exon 5 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele.

Development
A loxP site flanked targeting vector containing hygromycin resistance and thymidine kinase genes was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 5 of the targeted gene, and another loxP site was inserted upstream of exon 5. This construct was electroporated into 129S4/SvJae derived LW-1 embryonic stem (ES) cells, which were transiently transfected with a Cre-recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric animals were crossed to BALB/cAnNTac mice before being made homozygous.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying   Pten^tm1Hwu allele

006440	B6.129S4-Ptentm1Hwu/J
006068	STOCK Ptentm1Hwu/J

View Strains carrying   Pten^tm1Hwu     (2 strains)

Additional Web Information

Cre-lox Systems
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Pten^tm1Hwu/Pten⁺

        involves: 129S4/SvJae * BALB/c

• tumorigenesis
• abnormal tumor incidence (MGI Ref ID J:110567)
  • spectrum of tumor incidence and onset on the BALB/c background are similar to Pten^tm1.1Hwu on the BALB/c background in the first seven months

View Research Applications

Research Applications

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

Apoptosis Research
Endogenous Regulators

Cancer Research
Genes Regulating Growth and Proliferation

Cell Biology Research
Genes Regulating Growth and Proliferation

Research Tools
Apoptosis Research
Cancer Research
Cre-lox System (loxP-flanked Sequences)
Developmental Biology Research (Cre-lox System)

Pten^tm1Hwu related

Cancer Research
Tumor Suppressor Genes

Cell Biology Research
Cell Cycle Regulation

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ptentm1Hwu
Allele Name		targeted mutation 1, Hong Wu
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Ptenfl; Ptenflox; Ptenloxp;
Mutation Made By		Hong Wu,   UCLA
Strain of Origin		129S4/SvJae
ES Cell Line Name		LW1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Pten, phosphatase and tensin homolog
Chromosome		19
Gene Common Name(s)		10q23del; 2310035O07Rik; A130070J02Rik; AI463227; BZS; MGC11227; MHAM; MMAC1; Mmac; PTEN1; RIKEN cDNA 2310035O07 gene; RIKEN cDNA A130070J02 gene; TEP1; expressed sequence AI463227;
Molecular Note		A loxP flanked hygromycin resistance cassette was inserted 5' to exon 5, and a single loxP site was inserted 3' to exon 5, which encodes the phosphatase domain. The hygromycin cassette was removed in ES cells by transient Cre recombinase expression prior to the production of chimeric mice, leaving a single loxP site in place of the cassette. These insertions do not appear to have any effect on the normal function of the gene. [MGI Ref ID J:75117]

Genotyping

Genotyping Information

Genotyping Protocols

Pten^tm1Hwu, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Groszer M; Erickson R; Scripture-Adams DD; Lesche R; Trumpp A; Zack JA; Kornblum HI; Liu X; Wu H. 2001. Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294(5549):2186-9. [PubMed: 11691952]  [MGI Ref ID J:73255]

Additional References

Anzelon AN; Wu H; Rickert RC. 2003. Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function. Nat Immunol 4(3):287-94. [PubMed: 12563260]  [MGI Ref ID J:83213]

Lesche R; Groszer M; Gao J; Wang Y; Messing A; Sun H; Liu X; Wu H. 2002. Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis 32(2):148-9. [PubMed: 11857804]  [MGI Ref ID J:75117]

Li G; Robinson GW; Lesche R; Martinez-Diaz H; Jiang Z; Rozengurt N; Wagner KU; Wu DC; Lane TF; Liu X; Hennighausen L; Wu H. 2002. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 129(17):4159-70. [PubMed: 12163417]  [MGI Ref ID J:78415]

Stiles B; Wang Y; Stahl A; Bassilian S; Lee WP; Kim YJ; Sherwin R; Devaskar S; Lesche R; Magnuson MA; Wu H. 2004. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Proc Natl Acad Sci U S A 101(7):2082-7. [PubMed: 14769918]  [MGI Ref ID J:88441]

Pten^tm1Hwu related

Anzelon AN; Wu H; Rickert RC. 2003. Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function. Nat Immunol 4(3):287-94. [PubMed: 12563260]  [MGI Ref ID J:83213]

Berquin IM; Min Y; Wu R; Wu H; Chen YQ. 2005. Expression signature of the mouse prostate. J Biol Chem 280(43):36442-51. [PubMed: 16055444]  [MGI Ref ID J:106938]

Berquin IM; Min Y; Wu R; Wu J; Perry D; Cline JM; Thomas MJ; Thornburg T; Kulik G; Smith A; Edwards IJ; D'Agostino R; Zhang H; Wu H; Kang JX; Chen YQ. 2007. Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. J Clin Invest 117(7):1866-75. [PubMed: 17607361]  [MGI Ref ID J:124208]

Daikoku T; Hirota Y; Tranguch S; Joshi AR; DeMayo FJ; Lydon JP; Ellenson LH; Dey SK. 2008. Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice. Cancer Res 68(14):5619-27. [PubMed: 18632614]  [MGI Ref ID J:139053]

Daikoku T; Tranguch S; Trofimova IN; Dinulescu DM; Jacks T; Nikitin AY; Connolly DC; Dey SK. 2006. Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer. Cancer Res 66(5):2527-31. [PubMed: 16510568]  [MGI Ref ID J:106703]

Dinulescu DM; Ince TA; Quade BJ; Shafer SA; Crowley D; Jacks T. 2005. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 11(1):63-70. [PubMed: 15619626]  [MGI Ref ID J:96296]

Dourdin N; Schade B; Lesurf R; Hallett M; Munn RJ; Cardiff RD; Muller WJ. 2008. Phosphatase and tensin homologue deleted on chromosome 10 deficiency accelerates tumor induction in a mouse model of ErbB-2 mammary tumorigenesis. Cancer Res 68(7):2122-31. [PubMed: 18381417]  [MGI Ref ID J:133305]

Fan HY; Liu Z; Cahill N; Richards JS. 2008. Targeted disruption of pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells. Mol Endocrinol 22(9):2128-40. [PubMed: 18606860]  [MGI Ref ID J:138315]

Freeman D; Lesche R; Kertesz N; Wang S; Li G; Gao J; Groszer M; Martinez-Diaz H; Rozengurt N; Thomas G; Liu X; Wu H. 2006. Genetic background controls tumor development in PTEN-deficient mice. Cancer Res 66(13):6492-6. [PubMed: 16818619]  [MGI Ref ID J:110567]

Frew IJ; Minola A; Georgiev S; Hitz M; Moch H; Richard S; Vortmeyer AO; Krek W. 2008. Combined VHLH and PTEN mutation causes genital tract cystadenoma and squamous metaplasia. Mol Cell Biol 28(14):4536-48. [PubMed: 18474617]  [MGI Ref ID J:137442]

Frew IJ; Thoma CR; Georgiev S; Minola A; Hitz M; Montani M; Moch H; Krek W. 2008. pVHL and PTEN tumour suppressor proteins cooperatively suppress kidney cyst formation. EMBO J 27(12):1747-57. [PubMed: 18497742]  [MGI Ref ID J:137073]

Guo W; Lasky JL; Chang CJ; Mosessian S; Lewis X; Xiao Y; Yeh JE; Chen JY; Iruela-Arispe ML; Varella-Garcia M; Wu H. 2008. Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation. Nature 453(7194):529-33. [PubMed: 18463637]  [MGI Ref ID J:135172]

He XC; Yin T; Grindley JC; Tian Q; Sato T; Tao WA; Dirisina R; Porter-Westpfahl KS; Hembree M; Johnson T; Wiedemann LM; Barrett TA; Hood L; Wu H; Li L. 2007. PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet 39(2):189-98. [PubMed: 17237784]  [MGI Ref ID J:118329]

Hill R; Song Y; Cardiff RD; Van Dyke T. 2005. Heterogeneous tumor evolution initiated by loss of pRb function in a preclinical prostate cancer model. Cancer Res 65(22):10243-54. [PubMed: 16288012]  [MGI Ref ID J:103408]

Iwanaga K; Yang Y; Raso MG; Ma L; Hanna AE; Thilaganathan N; Moghaddam S; Evans CM; Li H; Cai WW; Sato M; Minna JD; Wu H; Creighton CJ; Demayo FJ; Wistuba II; Kurie JM. 2008. Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer. Cancer Res 68(4):1119-27. [PubMed: 18281487]  [MGI Ref ID J:131721]

Jia S; Liu Z; Zhang S; Liu P; Zhang L; Lee SH; Zhang J; Signoretti S; Loda M; Roberts TM; Zhao JJ. 2008. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 454(7205):776-9. [PubMed: 18594509]  [MGI Ref ID J:138565]

John GB; Gallardo TD; Shirley LJ; Castrillon DH. 2008. Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. Dev Biol 321(1):197-204. [PubMed: 18601916]  [MGI Ref ID J:138697]

Khodavirdi AC; Song Z; Yang S; Zhong C; Wang S; Wu H; Pritchard C; Nelson PS; Roy-Burman P. 2006. Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res 66(2):883-8. [PubMed: 16424021]  [MGI Ref ID J:106566]

Klein RD. 2005. The use of genetically engineered mouse models of prostate cancer for nutrition and cancer chemoprevention research. Mutat Res 576(1-2):111-9. [PubMed: 15885713]  [MGI Ref ID J:100619]

Klezovitch O; Risk M; Coleman I; Lucas JM; Null M; True LD; Nelson PS; Vasioukhin V. 2008. A causal role for ERG in neoplastic transformation of prostate epithelium. Proc Natl Acad Sci U S A 105(6):2105-10. [PubMed: 18245377]  [MGI Ref ID J:131932]

Kurlawalla-Martinez C; Stiles B; Wang Y; Devaskar SU; Kahn BB; Wu H. 2005. Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. Mol Cell Biol 25(6):2498-510. [PubMed: 15743841]  [MGI Ref ID J:97588]

Kwon CH; Zhao D; Chen J; Alcantara S; Li Y; Burns DK; Mason RP; Lee EY; Wu H; Parada LF. 2008. Pten haploinsufficiency accelerates formation of high-grade astrocytomas. Cancer Res 68(9):3286-94. [PubMed: 18451155]  [MGI Ref ID J:134611]

Lesche R; Groszer M; Gao J; Wang Y; Messing A; Sun H; Liu X; Wu H. 2002. Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis 32(2):148-9. [PubMed: 11857804]  [MGI Ref ID J:75117]

Li G; Robinson GW; Lesche R; Martinez-Diaz H; Jiang Z; Rozengurt N; Wagner KU; Wu DC; Lane TF; Liu X; Hennighausen L; Wu H. 2002. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 129(17):4159-70. [PubMed: 12163417]  [MGI Ref ID J:78415]

Liao CP; Zhong C; Saribekyan G; Bading J; Park R; Conti PS; Moats R; Berns A; Shi W; Zhou Z; Nikitin AY; Roy-Burman P. 2007. Mouse models of prostate adenocarcinoma with the capacity to monitor spontaneous carcinogenesis by bioluminescence or fluorescence. Cancer Res 67(15):7525-33. [PubMed: 17671224]  [MGI Ref ID J:123911]

Lu TL; Chang JL; Liang CC; You LR; Chen CM. 2007. Tumor spectrum, tumor latency and tumor incidence of the pten-deficient mice. PLoS ONE 2(11):e1237. [PubMed: 18043744]  [MGI Ref ID J:130367]

Omori SA; Cato MH; Anzelon-Mills A; Puri KD; Shapiro-Shelef M; Calame K; Rickert RC. 2006. Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling. Immunity 25(4):545-57. [PubMed: 17000121]  [MGI Ref ID J:114881]

Reddy P; Liu L; Adhikari D; Jagarlamudi K; Rajareddy S; Shen Y; Du C; Tang W; Hamalainen T; Peng SL; Lan ZJ; Cooney AJ; Huhtaniemi I; Liu K. 2008. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science 319(5863):611-3. [PubMed: 18239123]  [MGI Ref ID J:131827]

Squarize CH; Castilho RM; Gutkind JS. 2008. Chemoprevention and treatment of experimental Cowden's disease by mTOR inhibition with rapamycin. Cancer Res 68(17):7066-72. [PubMed: 18757421]  [MGI Ref ID J:138927]

Stanger BZ; Stiles B; Lauwers GY; Bardeesy N; Mendoza M; Wang Y; Greenwood A; Cheng KH; McLaughlin M; Brown D; Depinho RA; Wu H; Melton DA; Dor Y. 2005. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 8(3):185-95. [PubMed: 16169464]  [MGI Ref ID J:102226]

Stiles B; Wang Y; Stahl A; Bassilian S; Lee WP; Kim YJ; Sherwin R; Devaskar S; Lesche R; Magnuson MA; Wu H. 2004. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Proc Natl Acad Sci U S A 101(7):2082-7. [PubMed: 14769918]  [MGI Ref ID J:88441]

Stiles BL; Kuralwalla-Martinez C; Guo W; Gregorian C; Wang Y; Tian J; Magnuson MA; Wu H. 2006. Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes. Mol Cell Biol 26(7):2772-81. [PubMed: 16537919]  [MGI Ref ID J:106937]

Wang S; Gao J; Lei Q; Rozengurt N; Pritchard C; Jiao J; Thomas GV; Li G; Roy-Burman P; Nelson PS; Liu X; Wu H. 2003. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4(3):209-21. [PubMed: 14522255]  [MGI Ref ID J:93902]

Wang S; Garcia AJ; Wu M; Lawson DA; Witte ON; Wu H. 2006. Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci U S A 103(5):1480-5. [PubMed: 16432235]  [MGI Ref ID J:105995]

Xiao C; Srinivasan L; Calado DP; Patterson HC; Zhang B; Wang J; Henderson JM; Kutok JL; Rajewsky K. 2008. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9(4):405-14. [PubMed: 18327259]  [MGI Ref ID J:133215]

Xing Y; Li C; Hu L; Tiozzo C; Li M; Chai Y; Bellusci S; Anderson S; Minoo P. 2008. Mechanisms of TGFbeta inhibition of LUNG endodermal morphogenesis: the role of TbetaRII, Smads, Nkx2.1 and Pten. Dev Biol 320(2):340-50. [PubMed: 18602626]  [MGI Ref ID J:138200]

Xu X; Kobayashi S; Qiao W; Li C; Xiao C; Radaeva S; Stiles B; Wang RH; Ohara N; Yoshino T; LeRoith D; Torbenson MS; Gores GJ; Wu H; Gao B; Deng CX. 2006. Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice. J Clin Invest 116(7):1843-52. [PubMed: 16767220]  [MGI Ref ID J:111718]

Yang Y; Iwanaga K; Raso MG; Wislez M; Hanna AE; Wieder ED; Molldrem JJ; Wistuba II; Powis G; Demayo FJ; Kim CF; Kurie JM. 2008. Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer. PLoS ONE 3(5):e2220. [PubMed: 18493606]  [MGI Ref ID J:136369]

Yao D; Alexander CL; Quinn JA; Chan WC; Wu H; Greenhalgh DA. 2008. Fos cooperation with PTEN loss elicits keratoacanthoma not carcinoma, owing to p53/p21 WAF-induced differentiation triggered by GSK3beta inactivation and reduced AKT activity. J Cell Sci 121(Pt 10):1758-69. [PubMed: 18445683]  [MGI Ref ID J:138532]

Yao D; Alexander CL; Quinn JA; Porter MJ; Wu H; Greenhalgh DA. 2006. PTEN loss promotes rasHa-mediated papillomatogenesis via dual up-regulation of AKT activity and cell cycle deregulation but malignant conversion proceeds via PTEN-associated pathways. Cancer Res 66(3):1302-12. [PubMed: 16452183]  [MGI Ref ID J:106683]

Yilmaz OH; Valdez R; Theisen BK; Guo W; Ferguson DO; Wu H; Morrison SJ. 2006. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441(7092):475-82. [PubMed: 16598206]  [MGI Ref ID J:109085]

Yoo LI; Liu DW; Le Vu S; Bronson RT; Wu H; Yuan J. 2006. Pten deficiency activates distinct downstream signaling pathways in a tissue-specific manner. Cancer Res 66(4):1929-39. [PubMed: 16488991]  [MGI Ref ID J:106662]

Yue Q; Groszer M; Gil JS; Berk AJ; Messing A; Wu H; Liu X. 2005. PTEN deletion in Bergmann glia leads to premature differentiation and affects laminar organization. Development 132(14):3281-91. [PubMed: 15944184]  [MGI Ref ID J:100428]

Zeiser R; Leveson-Gower DB; Zambricki EA; Kambham N; Beilhack A; Loh J; Hou JZ; Negrin RS. 2008. Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells. Blood 111(1):453-62. [PubMed: 17967941]  [MGI Ref ID J:130295]

Zhang J; Grindley JC; Yin T; Jayasinghe S; He XC; Ross JT; Haug JS; Rupp D; Porter-Westpfahl KS; Wiedemann LM; Wu H; Li L. 2006. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441(7092):518-22. [PubMed: 16633340]  [MGI Ref ID J:109084]

Zhong C; Saribekyan G; Liao CP; Cohen MB; Roy-Burman P. 2006. Cooperation between FGF8b overexpression and PTEN deficiency in prostate tumorigenesis. Cancer Res 66(4):2188-94. [PubMed: 16489020]  [MGI Ref ID J:106650]

Zhu D; Hattori H; Jo H; Jia Y; Subramanian KK; Loison F; You J; Le Y; Honczarenko M; Silberstein L; Luo HR. 2006. Deactivation of phosphatidylinositol 3,4,5-trisphosphate/Akt signaling mediates neutrophil spontaneous death. Proc Natl Acad Sci U S A 103(40):14836-41. [PubMed: 16988010]  [MGI Ref ID J:114699]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice are bred.
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
	None Available
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.

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Ordering and Purchasing Information

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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

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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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.

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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.