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| These CX3CR1-GFP mice express EGFP under control of the endogenous Cx3cr1 locus and may be useful in studies of leukocyte migration and trafficking, as well as for transplantation studies. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Generation N10+N1F6 (08-JAN-08) Donating Investigator Dan Littman, New York University Medical Center Description
Mice that are homozygous for the CX3CR1-GFP targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. RT-PCR analysis of lymphoid tissue from homozygotes detects mutant gene product (mRNA) and no wild type gene product (mRNA). Flow cytometric analysis of peripheral blood cells identified a subset of green fluorescent cells not observed in wild type mice. Enhanced Green Fluorescent Protein (EGFP), but not the endogenous gene, is expressed in monocytes, dendritic cells, NK cells, and brain microglia, mimicking endogenous gene expression. The same subset of peripheral blood cells isolated from heterozygote mice express detectable levels of EGFP. Immunohistochemical analysis of spleen and peripheral nerve tissue from homozygotes does not detect EGFP. These CX3CR1-GFP mutant mice may be useful in studies of leukocyte migration and trafficking, as well as for transplantation studies.Of note, CX3CR1-GFP mice are also available harboring with the CD45.1 (Ly5.1 or Ptprca) allele, which is atypical for the C57BL/6 congenic background (see Stock No. 008451).
Development
A targeting vector containing an Enhanced Green Fluorescent Protein (EGFP, Clontech) cDNA sequence, loxP-flanked neomycin resistance gene, herpes simplex virus thymidine kinase gene, and SV40 polyadenylation site sequence was used to disrupt the first 390 bp of exon 2. The construct was electroporated into 129P2/OlaHsd derived E14.1 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. ES cells that had successfully undergone Cre-mediated recombination (removing the loxP-flanked neo cassette and leaving a single loxP site downstream of EGFP) were injected into recipient blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 for 10 generations before being made homozygous. During the backcross, mice were likely bred to a B6.CD45.1 congenic strain (harboring the CD45.1 (Ly5.1 or Ptprca) allele rather than the CD45.2 (Ly5.2 or Ptprcb) allele normally present in C57BL/6 mice). These mice, however, were bred such that they still harbor the expected CD45.2 (Ly5.2 or Ptprcb) allele normally present in C57BL/6 mice.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (170 strains)
008451 B6.129P(Cg)-Ptprca Cx3cr1tm1Litt/LittJ
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Cx3cr1tm1Litt/Cx3cr1tm1Litt
involves: 129P2/OlaHsd * C57BL/6
- vision/eye phenotype
- abnormal retina morphology (MGI Ref ID J:127548)
- subretinal microglial cells accumulate with age in the retina unlike in wild-type mice
- following laser injury, more subretinal microglial cells accumulate adjacent to the choroid scar than in heterozygous mice at 7 and 14 days post injury
- choroidal neovascularization (MGI Ref ID J:127548)
- following laser injury, more subretinal microglial cells accumulate adjacent to the choroid scar than in similarly treated wild-type mice and choroid neovascularization is twice as much as in similarly treated wild-type mice
- immune system phenotype
- *normal* immune system phenotype (MGI Ref ID J:84544)
- normal dendritic cell migration and IL-12 production in response to a microbial antigen (STAg)
- normal Langerhans cell migration and APC function in response to contact sensitizer (oxazolone)
- nervous system phenotype
- *normal* nervous system phenotype (MGI Ref ID J:84544)
- normal neuronal-glial cross talk indicated by microglial response to peripheral nerve injury, 129P2/OlaHsd and C57BL/6 mixed genetic background
- cardiovascular system phenotype
- choroidal neovascularization (MGI Ref ID J:127548)
- following laser injury, more subretinal microglial cells accumulate adjacent to the choroid scar than in similarly treated wild-type mice and choroid neovascularization is twice as much as in similarly treated wild-type mice
Cx3cr1tm1Litt/Cx3cr1tm1Litt
C.129P2-Cx3cr1tm1Litt
- immune system phenotype
- *normal* immune system phenotype (MGI Ref ID J:84544)
- normal monocyte extravasation and subsequent differentiation into macrophages in response to intraperitoneal injection of thioglycolate, a model of acute peritonitis
This mouse can be used to support research in many areas including:
GFP relatedCancer Research
Growth Factors/Receptors/Cytokines
Toxicology (xenograft/transplant host)
Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Immunodeficiency (NK Cell Deficiency)
Research Tools
Cancer Research (B, T, and NK cell deficiency) (xenograft/transplant host)
Cancer Research (xenograft/transplant host)
Cell Biology Research
Developmental Biology Research (transplantation marker for embryonic and adult tissue)
Fluorescent Proteins
Genetics Research (Tissue/Cell Markers: cell marker for bone marrow transplantation)
Genetics Research (Tissue/Cell Markers: glial cells)
Genetics Research (Tissue/Cell Markers: multiple)
Genetics Research (Tissue/Cell Markers: neurons)
Genetics Research (Tissue/Cell Markers: transplantation marker for embryonic and adult tissue)
Immunology and Inflammation Research (NK Cell Deficiency)
Immunology and Inflammation Research
Neurobiology Research (cell marker)
Toxicology Research (xenograft/transplant host)
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Cx3cr1tm1Litt | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Dan R Littman | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | CX3CR1-GFP; CX3CR1-; CX3CR1GFP; | ||
| Mutation Made By | Steffen Jung, Weizmann Institute of Science | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14.1 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Site of Expression | EGFP expression mimics endogenous gene expression and is detected in monocytes, dendritic cells, NK cells, and brain microglia. | ||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Gene Symbol and Name | Cx3cr1, chemokine (C-X3-C) receptor 1 | ||
| Chromosome | 9 | ||
| Gene Common Name(s) | CCRL1; CMKBRL1; CMKDR1; GPR13; GPRV28; Rbs11; V28; | ||
| Molecular Note | The endogenous locus was disrupted by the insertion of sequence encoding green fluourescent protein (GFP), replacing the first 390 bp of the coding exon (exon 2). The deleted region encoded an amino-terminal portion of the protein that is crucial for interaction with endogenous ligand, Cx3cl1. A floxed neo gene included in the targeting vector for selection was excised prior to germline transmission, leaving a single loxP site downstream of the GFP sequence. RT-PCR and flow cytometry indicated an absenceof endogenous protein and the presence GFP expression in homozygous mutant mice. [MGI Ref ID J:84544] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Cx3cr1tm1Litt, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Jung S; Aliberti J; Graemmel P; Sunshine MJ; Kreutzberg GW; Sher A; Littman DR. 2000. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20(11):4106-14. [PubMed: 10805752] [MGI Ref ID J:84544]
Additional References
Cx3cr1tm1Litt relatedArnold L; Henry A; Poron F; Baba-Amer Y; van Rooijen N; Plonquet A; Gherardi RK; Chazaud B. 2007. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 204(5):1057-69. [PubMed: 17485518] [MGI Ref ID J:125715]
Bertrand JY; Jalil A; Klaine M; Jung S; Cumano A; Godin I. 2005. Three pathways to mature macrophages in the early mouse yolk sac. Blood 106(9):3004-11. [PubMed: 16020514] [MGI Ref ID J:123941]
Cardona AE; Pioro EP; Sasse ME; Kostenko V; Cardona SM; Dijkstra IM; Huang D; Kidd G; Dombrowski S; Dutta R; Lee JC; Cook DN; Jung S; Lira SA; Littman DR; Ransohoff RM. 2006. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9(7):917-24. [PubMed: 16732273] [MGI Ref ID J:110266]
Cardona AE; Sasse ME; Liu L; Cardona SM; Mizutani M; Savarin C; Hu T; Ransohoff RM. 2008. Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues. Blood 112(2):256-63. [PubMed: 18347198] [MGI Ref ID J:138467]
Carreras E; Turner S; Paharkova-Vatchkova V; Mao A; Dascher C; Kovats S. 2008. Estradiol acts directly on bone marrow myeloid progenitors to differentially regulate GM-CSF or Flt3 ligand-mediated dendritic cell differentiation. J Immunol 180(2):727-38. [PubMed: 18178810] [MGI Ref ID J:130951]
Chinnery HR; Ruitenberg MJ; Plant GW; Pearlman E; Jung S; McMenamin PG. 2007. The chemokine receptor CX3CR1 mediates homing of MHC class II-positive cells to the normal mouse corneal epithelium. Invest Ophthalmol Vis Sci 48(4):1568-74. [PubMed: 17389486] [MGI Ref ID J:123257]
Combadiere C; Feumi C; Raoul W; Keller N; Rodero M; Pezard A; Lavalette S; Houssier M; Jonet L; Picard E; Debre P; Sirinyan M; Deterre P; Ferroukhi T; Cohen SY; Chauvaud D; Jeanny JC; Chemtob S; Behar-Cohen F; Sennlaub F. 2007. CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. J Clin Invest 117(10):2920-8. [PubMed: 17909628] [MGI Ref ID J:127548]
Fainaru O; Woolf E; Lotem J; Yarmus M; Brenner O; Goldenberg D; Negreanu V; Bernstein Y; Levanon D; Jung S; Groner Y. 2004. Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation. EMBO J 23(4):969-79. [PubMed: 14765120] [MGI Ref ID J:88424]
Geissmann F; Jung S; Littman DR. 2003. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1):71-82. [PubMed: 12871640] [MGI Ref ID J:90912]
Hapfelmeier S; Muller AJ; Stecher B; Kaiser P; Barthel M; Endt K; Eberhard M; Robbiani R; Jacobi CA; Heikenwalder M; Kirschning C; Jung S; Stallmach T; Kremer M; Hardt WD. 2008. Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent step in DeltainvG S. Typhimurium colitis. J Exp Med 205(2):437-50. [PubMed: 18268033] [MGI Ref ID J:132107]
Haynes SE; Hollopeter G; Yang G; Kurpius D; Dailey ME; Gan WB; Julius D. 2006. The P2Y(12) receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9(12):1512-9. [PubMed: 17115040] [MGI Ref ID J:116110]
Huang D; Shi FD; Jung S; Pien GC; Wang J; Salazar-Mather TP; He TT; Weaver JT; Ljunggren HG; Biron CA; Littman DR; Ransohoff RM. 2006. The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system. FASEB J 20(7):896-905. [PubMed: 16675847] [MGI Ref ID J:129712]
Huang D; Wujek J; Kidd G; He TT; Cardona A; Sasse ME; Stein EJ; Kish J; Tani M; Charo IF; Proudfoot AE; Rollins BJ; Handel T; Ransohoff RM. 2005. Chronic expression of monocyte chemoattractant protein-1 in the central nervous system causes delayed encephalopathy and impaired microglial function in mice. FASEB J 19(7):761-72. [PubMed: 15857890] [MGI Ref ID J:134548]
Kezic J; McMenamin PG. 2008. Differential turnover rates of monocyte-derived cells in varied ocular tissue microenvironments. J Leukoc Biol 84(3):721-9. [PubMed: 18577714] [MGI Ref ID J:138301]
Kezic J; Xu H; Chinnery HR; Murphy CC; McMenamin PG. 2008. Retinal microglia and uveal tract dendritic cells and macrophages are not CX3CR1 dependent in their recruitment and distribution in the young mouse eye. Invest Ophthalmol Vis Sci 49(4):1599-608. [PubMed: 18385080] [MGI Ref ID J:136154]
Kim JV; Dustin ML. 2006. Innate response to focal necrotic injury inside the blood-brain barrier. J Immunol 177(8):5269-77. [PubMed: 17015712] [MGI Ref ID J:139445]
Lauro C; Di Angelantonio S; Cipriani R; Sobrero F; Antonilli L; Brusadin V; Ragozzino D; Limatola C. 2008. Activity of adenosine receptors type 1 Is required for CX3CL1-mediated neuroprotection and neuromodulation in hippocampal neurons. J Immunol 180(11):7590-6. [PubMed: 18490761] [MGI Ref ID J:136344]
Lin KL; Suzuki Y; Nakano H; Ramsburg E; Gunn MD. 2008. CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J Immunol 180(4):2562-72. [PubMed: 18250467] [MGI Ref ID J:131979]
Liu P; Patil S; Rojas M; Fong AM; Smyth SS; Patel DD. 2006. CX3CR1 deficiency confers protection from intimal hyperplasia after arterial injury. Arterioscler Thromb Vasc Biol 26(9):2056-62. [PubMed: 16809547] [MGI Ref ID J:124722]
Masse GX; Corcuff E; Strick-Marchand H; Guy-Grand D; Tafuri-Bladt A; Albert ML; Lantz O; Di Santo JP. 2007. Gamma c cytokines condition the progressive differentiation of CD4+ T cells. Proc Natl Acad Sci U S A 104(39):15442-7. [PubMed: 17855567] [MGI Ref ID J:125207]
McComb JG; Ranganathan M; Liu XH; Pilewski JM; Ray P; Watkins SC; Choi AM; Lee JS. 2008. CX3CL1 up-regulation is associated with recruitment of CX3CR1+ mononuclear phagocytes and T lymphocytes in the lungs during cigarette smoke-induced emphysema. Am J Pathol 173(4):949-61. [PubMed: 18772344] [MGI Ref ID J:139658]
Meyer-Luehmann M; Spires-Jones TL; Prada C; Garcia-Alloza M; de Calignon A; Rozkalne A; Koenigsknecht-Talboo J; Holtzman DM; Bacskai BJ; Hyman BT. 2008. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 451(7179):720-4. [PubMed: 18256671] [MGI Ref ID J:132628]
Mueller-Steiner S; Zhou Y; Arai H; Roberson ED; Sun B; Chen J; Wang X; Yu G; Esposito L; Mucke L; Gan L. 2006. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron 51(6):703-14. [PubMed: 16982417] [MGI Ref ID J:113649]
Nahrendorf M; Swirski FK; Aikawa E; Stangenberg L; Wurdinger T; Figueiredo JL; Libby P; Weissleder R; Pittet MJ. 2007. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204(12):3037-47. [PubMed: 18025128] [MGI Ref ID J:128499]
Niess JH; Brand S; Gu X; Landsman L; Jung S; McCormick BA; Vyas JM; Boes M; Ploegh HL; Fox JG; Littman DR; Reinecker HC. 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307(5707):254-8. [PubMed: 15653504] [MGI Ref ID J:95694]
Qu C; Edwards EW; Tacke F; Angeli V; Llodra J; Sanchez-Schmitz G; Garin A; Haque NS; Peters W; van Rooijen N; Sanchez-Torres C; Bromberg J; Charo IF; Jung S; Lira SA; Randolph GJ. 2004. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. J Exp Med 200(10):1231-41. [PubMed: 15534368] [MGI Ref ID J:94536]
Sapoznikov A; Pewzner-Jung Y; Kalchenko V; Krauthgamer R; Shachar I; Jung S. 2008. Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches. Nat Immunol 9(4):388-95. [PubMed: 18311142] [MGI Ref ID J:133263]
Sawanobori Y; Ueha S; Kurachi M; Shimaoka T; Talmadge JE; Abe J; Shono Y; Kitabatake M; Kakimi K; Mukaida N; Matsushima K. 2008. Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood 111(12):5457-66. [PubMed: 18375791] [MGI Ref ID J:136844]
Soehnlein O; Zernecke A; Eriksson EE; Rothfuchs AG; Pham CT; Herwald H; Bidzhekov K; Rottenberg ME; Weber C; Lindbom L. 2008. Neutrophil secretion products pave the way for inflammatory monocytes. Blood 112(4):1461-71. [PubMed: 18490516] [MGI Ref ID J:138439]
Synowitz M; Glass R; Farber K; Markovic D; Kronenberg G; Herrmann K; Schnermann J; Nolte C; van Rooijen N; Kiwit J; Kettenmann H. 2006. A1 adenosine receptors in microglia control glioblastoma-host interaction. Cancer Res 66(17):8550-7. [PubMed: 16951167] [MGI Ref ID J:112410]
Tacke F; Alvarez D; Kaplan TJ; Jakubzick C; Spanbroek R; Llodra J; Garin A; Liu J; Mack M; van Rooijen N; Lira SA; Habenicht AJ; Randolph GJ. 2007. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 117(1):185-94. [PubMed: 17200718] [MGI Ref ID J:117437]
Thomas DM; Francescutti-Verbeem DM; Kuhn DM. 2008. Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling. J Neurochem 106(2):696-705. [PubMed: 18410508] [MGI Ref ID J:139390]
Vallon-Eberhard A; Landsman L; Yogev N; Verrier B; Jung S. 2006. Transepithelial pathogen uptake into the small intestinal lamina propria. J Immunol 176(4):2465-9. [PubMed: 16456006] [MGI Ref ID J:106225]
Varol C; Landsman L; Fogg DK; Greenshtein L; Gildor B; Margalit R; Kalchenko V; Geissmann F; Jung S. 2007. Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med 204(1):171-80. [PubMed: 17190836] [MGI Ref ID J:125312]
Wojcik AJ; Skaflen MD; Srinivasan S; Hedrick CC. 2008. A Critical Role for ABCG1 in Macrophage Inflammation and Lung Homeostasis. J Immunol 180(6):4273-82. [PubMed: 18322240] [MGI Ref ID J:132952]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as homozygotes. Mating System Homozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.30 Female or Male Homozygous for Cx3cr1tm1Litt *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.60 Homozygous for Cx3cr1tm1Litt x Homozygous for Cx3cr1tm1Litt
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $263.00 Female or Male Homozygous for Cx3cr1tm1Litt *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $526.00 Homozygous for Cx3cr1tm1Litt x Homozygous for Cx3cr1tm1Litt
Additional Supply Details
| Supply Notes |
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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. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| 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
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Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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