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| Tamoxifen administration in these mice induces Cre recombinase expression in all cells of the mouse limb that express the endogenous gene. Cells that contribute to more anterior digits cease to express Shh at an earlier stage of limb development.This mutant mouse strain may be useful in studies of limb patterning and development. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Former Names B6.129S-Shhtm2(cre/ERT2)Cjt/J (Changed: 30-MAR-10 ) B6.129S-Shhtm2(cre/ESR1)Cjt/J (Changed: 30-MAR-10 ) 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 +/+ sibling x Heterozygote (Female x Male) 29-AUG-06 Species laboratory mouse Generation N5+N1F14 (30-APR-13)
Generation DefinitionsDonating Investigator Clifford J Tabin, Harvard Medical School Description
This strain expresses a fusion product involving Cre recombinase and a mutant form of the human estrogen receptor ligand binding domain from the endogenous Shh locus. The mutant human estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Restricted to the cytoplasm, the Cre/ESR1 protein can only gain access to the nuclear compartment after exposure to tamoxifen. Tamoxifen administration induces Cre recombinase expression in all cells of the mouse limb that express the endogenous gene resulting in the deletion of the first 35 base pairs following the ATG. Introduction of tamoxifen at E10.5 resulted in the labeling of LacZ-positive cells that contributed to digit 5 and the posterior half of digit 4 in E14.5 limbs. Injection of tamoxifen at E11.5 resulted in the labeling of cells only in digit 5. Homozygous mice are not viable or fertile. Heterozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of limb patterning and development.Development
A targeting vector containing a fusion product involving Cre recombinase and a mutant form of the human estrogen receptor ligand binding domain was inserted at the ATG of Shh. The construct was electroporated into 129S6/SvEv-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The donating investigator reported that the resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 5 generations (see SNP note below).A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Shh
000214 B10.D2/nSn-ShhHx/J 008466 B6.129X1(Cg)-Shhtm6Amc/J 005622 B6.Cg-Shhtm1(EGFP/cre)Cjt/J 004293 B6;129-Shhtm2Amc/J 011031 B6;129S4-Shhtm1.1Rseg/J 003318 STOCK Shhtm1Amc/J View Strains carrying other alleles of Shh (6 strains)
Additional Web Information
Introduction to Cre-lox technology
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Holoprosencephaly 3; HPE3 (SHH)
Microphthalmia, Isolated, with Coloboma 5; MCOPCB5 (SHH)
Schizencephaly (SHH)
Solitary Median Maxillary Central Incisor; SMMCI (SHH)
This mouse can be used to support research in many areas including:
cre relatedDevelopmental Biology Research
Embryonic Lethality (Homozygous)
Limb Patterning Defects
Skeletal Defects
Research Tools
Cre-lox System
Cre Recombinase Expression
Cre Recombinase Expression: Inducible
Developmental Biology Research
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Research Tools
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Shhtm2(cre/ERT2)Cjt | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Clifford J Tabin | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Shh-cre; ShhCreER; ShhCreERT2; ShhCreesr; Shhtm2(cre-ERT2)Cjt; Shhtm2(cre/ESR1)Cjt; ShhCreER; ShhcreERT2; | ||
| Mutation Made By | Clifford Tabin, Harvard Medical School | ||
| Strain of Origin | 129S6/SvEvTac | ||
| ES Cell Line Name | TC1/TC-1 | ||
| ES Cell Line Strain | 129S6/SvEvTac | ||
| Site of Expression | tamoxifen inducible Cre recombinase protein fused to a mutant form of the human estrogen receptor ligand binding domain; expression in all cells that express the Shh gene | ||
| Expressed Gene | cre, cre recombinase, bacteriophage P1 | ||
| Cre recombinase is an enzyme derived from the bacteriophage P1 that specifically recognizes loxP sites. Cre has been shown to effectively mediate the excision of DNA located between loxP sites. After the excision event, the DNA ends recombine leaving a single loxP site in place of the intervening sequence. | |||
| Driver Note | Shh | ||
| Inducible Note | induced by tamoxifen | ||
| Molecular Note | A cassette containing CreERT2 was inserted at the ATG. Upon recombination, the first 35 base pairs after the ATG were deleted. Cre was produced in all cells in which the endogenous mRNA was normally expressed. [MGI Ref ID J:92504] | ||
| Gene Symbol and Name | Shh, sonic hedgehog | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | Dsh; HHG1; HLP3; HPE3; Hhg1; Hx; Hxl3; M100081; MCOPCB5; SMMCI; TPT; TPTPS; hedgehog gene 1; hemimelic extra toes; hemimelic extratoes like 3; short digits; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Shhtm2(cre/ESR1)Cjt, Melt Curve Analysis
Shhtm2(cre/ESR1)Cjt, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Harfe BD; Scherz PJ; Nissim S; Tian H; McMahon AP; Tabin CJ. 2004. Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell 118(4):517-28. [PubMed: 15315763] [MGI Ref ID J:92504]
Additional References
Shhtm2(cre/ERT2)Cjt relatedAhn Y; Sanderson BW; Klein OD; Krumlauf R. 2010. Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning. Development 137(19):3221-31. [PubMed: 20724449] [MGI Ref ID J:168361]
Bell SM; Zhang L; Xu Y; Besnard V; Wert SE; Shroyer N; Whitsett JA. 2013. Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium. Dev Biol 375(2):128-39. [PubMed: 23266329] [MGI Ref ID J:194289]
Cai Y; Zhang Q; Wang C; Zhang Y; Ma T; Zhou X; Tian M; Rubenstein JL; Yang Z. 2013. Nuclear receptor COUP-TFII-expressing neocortical interneurons are derived from the medial and lateral/caudal ganglionic eminence and define specific subsets of mature interneurons. J Comp Neurol 521(2):479-97. [PubMed: 22791192] [MGI Ref ID J:193583]
Carney RS; Mangin JM; Hayes L; Mansfield K; Sousa VH; Fishell G; Machold RP; Ahn S; Gallo V; Corbin JG. 2010. Sonic hedgehog expressing and responding cells generate neuronal diversity in the medial amygdala. Neural Dev 5:14. [PubMed: 20507551] [MGI Ref ID J:161400]
Chen J; Krasnow MA. 2012. Integrin Beta 1 suppresses multilayering of a simple epithelium. PLoS One 7(12):e52886. [PubMed: 23285215] [MGI Ref ID J:195745]
Choi KS; Harfe BD. 2011. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs. Proc Natl Acad Sci U S A 108(23):9484-9. [PubMed: 21606373] [MGI Ref ID J:173333]
Choi KS; Lee C; Harfe BD. 2012. Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs. Mech Dev 129(9-12):255-62. [PubMed: 22841806] [MGI Ref ID J:188787]
Devenport D; Fuchs E. 2008. Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol 10(11):1257-68. [PubMed: 18849982] [MGI Ref ID J:145627]
Garcia AD; Petrova R; Eng L; Joyner AL. 2010. Sonic hedgehog regulates discrete populations of astrocytes in the adult mouse forebrain. J Neurosci 30(41):13597-608. [PubMed: 20943901] [MGI Ref ID J:165495]
Goddeeris MM; Rho S; Petiet A; Davenport CL; Johnson GA; Meyers EN; Klingensmith J. 2008. Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart. Development 135(10):1887-95. [PubMed: 18441277] [MGI Ref ID J:134643]
Greco V; Chen T; Rendl M; Schober M; Pasolli HA; Stokes N; Dela Cruz-Racelis J; Fuchs E. 2009. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell 4(2):155-69. [PubMed: 19200804] [MGI Ref ID J:149690]
Guha A; Vasconcelos M; Cai Y; Yoneda M; Hinds A; Qian J; Li G; Dickel L; Johnson JE; Kimura S; Guo J; McMahon J; McMahon AP; Cardoso WV. 2012. Neuroepithelial body microenvironment is a niche for a distinct subset of Clara-like precursors in the developing airways. Proc Natl Acad Sci U S A 109(31):12592-7. [PubMed: 22797898] [MGI Ref ID J:188519]
Haraguchi R; Matsumaru D; Nakagata N; Miyagawa S; Suzuki K; Kitazawa S; Yamada G. 2012. The hedgehog signal induced modulation of bone morphogenetic protein signaling: an essential signaling relay for urinary tract morphogenesis. PLoS One 7(7):e42245. [PubMed: 22860096] [MGI Ref ID J:189675]
Harris-Johnson KS; Domyan ET; Vezina CM; Sun X. 2009. beta-Catenin promotes respiratory progenitor identity in mouse foregut. Proc Natl Acad Sci U S A 106(38):16287-92. [PubMed: 19805295] [MGI Ref ID J:153236]
Jadhav AP; Cho SH; Cepko CL. 2006. Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property. Proc Natl Acad Sci U S A 103(50):18998-9003. [PubMed: 17148603] [MGI Ref ID J:118372]
King P; Paul A; Laufer E. 2009. Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. Proc Natl Acad Sci U S A 106(50):21185-90. [PubMed: 19955443] [MGI Ref ID J:155826]
Lapouge G; Youssef KK; Vokaer B; Achouri Y; Michaux C; Sotiropoulou PA; Blanpain C. 2011. Identifying the cellular origin of squamous skin tumors. Proc Natl Acad Sci U S A 108(18):7431-6. [PubMed: 21502497] [MGI Ref ID J:172048]
Lin C; Fisher AV; Yin Y; Maruyama T; Veith GM; Dhandha M; Huang GJ; Hsu W; Ma L. 2011. The inductive role of Wnt-beta-Catenin signaling in the formation of oral apparatus. Dev Biol 356(1):40-50. [PubMed: 21600200] [MGI Ref ID J:175262]
Lin C; Yin Y; Long F; Ma L. 2008. Tissue-specific requirements of beta-catenin in external genitalia development. Development 135(16):2815-25. [PubMed: 18635608] [MGI Ref ID J:139251]
Lin C; Yin Y; Veith GM; Fisher AV; Long F; Ma L. 2009. Temporal and spatial dissection of Shh signaling in genital tubercle development. Development 136(23):3959-67. [PubMed: 19906863] [MGI Ref ID J:158288]
Matsumaru D; Haraguchi R; Miyagawa S; Motoyama J; Nakagata N; Meijlink F; Yamada G. 2011. Genetic analysis of Hedgehog signaling in ventral body wall development and the onset of omphalocele formation. PLoS One 6(1):e16260. [PubMed: 21283718] [MGI Ref ID J:169568]
McGlinn E; Richman JM; Metzis V; Town L; Butterfield NC; Wainwright BJ; Wicking C. 2008. Expression of the NET family member Zfp503 is regulated by hedgehog and BMP signaling in the limb. Dev Dyn 237(4):1172-82. [PubMed: 18351672] [MGI Ref ID J:132977]
Miyagawa S; Moon A; Haraguchi R; Inoue C; Harada M; Nakahara C; Suzuki K; Matsumaru D; Kaneko T; Matsuo I; Yang L; Taketo MM; Iguchi T; Evans SM; Yamada G. 2009. Dosage-dependent hedgehog signals integrated with Wnt/{beta}-catenin signaling regulate external genitalia formation as an appendicular program. Development 136(23):3969-78. [PubMed: 19906864] [MGI Ref ID J:154979]
Miyagawa S; Satoh Y; Haraguchi R; Suzuki K; Iguchi T; Taketo MM; Nakagata N; Matsumoto T; Takeyama KI; Kato S; Yamada G. 2009. Genetic interactions of the Androgen and Wnt/{beta}-catenin Pathways for the Masculinization of External Genitalia. Mol Endocrinol 23(6):871-880. [PubMed: 19282366] [MGI Ref ID J:148515]
Morimoto M; Liu Z; Cheng HT; Winters N; Bader D; Kopan R. 2010. Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate. J Cell Sci 123(Pt 2):213-24. [PubMed: 20048339] [MGI Ref ID J:156690]
Nielsen CM; Dymecki SM. 2010. Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus. Dev Biol 340(2):430-7. [PubMed: 20123094] [MGI Ref ID J:160263]
Schuller U; Heine VM; Mao J; Kho AT; Dillon AK; Han YG; Huillard E; Sun T; Ligon AH; Qian Y; Ma Q; Alvarez-Buylla A; McMahon AP; Rowitch DH; Ligon KL. 2008. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14(2):123-34. [PubMed: 18691547] [MGI Ref ID J:139574]
Seifert AW; Bouldin CM; Choi KS; Harfe BD; Cohn MJ. 2009. Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development. Development 136(23):3949-57. [PubMed: 19906862] [MGI Ref ID J:154980]
Shin K; Lee J; Guo N; Kim J; Lim A; Qu L; Mysorekar IU; Beachy PA. 2011. Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472(7341):110-4. [PubMed: 21389986] [MGI Ref ID J:170991]
Thirumangalathu S; Harlow DE; Driskell AL; Krimm RF; Barlow LA. 2009. Fate mapping of mammalian embryonic taste bud progenitors. Development 136(9):1519-28. [PubMed: 19363153] [MGI Ref ID J:147959]
Tsao PN; Vasconcelos M; Izvolsky KI; Qian J; Lu J; Cardoso WV. 2009. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development 136(13):2297-307. [PubMed: 19502490] [MGI Ref ID J:150051]
Verheyden JM; Sun X. 2008. An Fgf/Gremlin inhibitory feedback loop triggers termination of limb bud outgrowth. Nature 454(7204):638-41. [PubMed: 18594511] [MGI Ref ID J:138578]
White AC; Tran K; Khuu J; Dang C; Cui Y; Binder SW; Lowry WE. 2011. Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proc Natl Acad Sci U S A 108(18):7425-30. [PubMed: 21502519] [MGI Ref ID J:172216]
Youssef KK; Van Keymeulen A; Lapouge G; Beck B; Michaux C; Achouri Y; Sotiropoulou PA; Blanpain C. 2010. Identification of the cell lineage at the origin of basal cell carcinoma. Nat Cell Biol 12(3):299-305. [PubMed: 20154679] [MGI Ref ID J:195334]
Zhang Z; Verheyden JM; Hassell JA; Sun X. 2009. FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb buds. Dev Cell 16(4):607-13. [PubMed: 19386269] [MGI Ref ID J:149477]
Zhu J; Mackem S. 2011. Analysis of mutants with altered shh activity and posterior digit loss supports a biphasic model for shh function as a morphogen and mitogen. Dev Dyn 240(5):1303-10. [PubMed: 21509901] [MGI Ref ID J:170964]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number FGB29
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice are bred to wildtype siblings (or C57BL/6J). Homozygous mice are not viable. Mating System +/+ sibling x Heterozygote (Female x Male) 29-AUG-06 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Heterozygous for Shhtm2(cre/ERT2)Cjt
Price per Pair (US dollars $) Pair Genotype $302.00 Heterozygous for Shhtm2(cre/ERT2)Cjt x Wild-type for Shhtm2(cre/ERT2)Cjt $302.00 Wild-type for Shhtm2(cre/ERT2)Cjt x Heterozygous for Shhtm2(cre/ERT2)Cjt Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along 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. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Heterozygous for Shhtm2(cre/ERT2)Cjt
Price per Pair (US dollars $) Pair Genotype $392.60 Heterozygous for Shhtm2(cre/ERT2)Cjt x Wild-type for Shhtm2(cre/ERT2)Cjt $392.60 Wild-type for Shhtm2(cre/ERT2)Cjt x Heterozygous for Shhtm2(cre/ERT2)Cjt Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along 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. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
|
|
|
Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along 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. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 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.Ordering Information
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