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 Background Strain C57BL/6 Donor Strain 129S4 via J1 ES cell line Generation N10F?+F15N1F3 (04-DEC-07)   Donating Investigator Arlene Sharpe,   Brigham and Women's Hospital

Description
Cd86 (B7-2) null mice are viable and fertile. Unimmunized mice have normal levels of serum immunoglobulin and normal numbers of B and T lymphocytes. Upon intravenous immunization without adjuvant, they fail to form germinal centers or undergo isotype switching and antigen specific IgG1 and IgG2a isotypes are found to be 5% that of wild type levels. When the immunization route is subcutaneous, IgG1 and IgG2a levels are the same as in wild type mice.

Development
A targeting vector containing a neomycin gene under the control of the mouse phosphoglycerol kinase (PGK) promoter was used to disrupt the exon encoding the Ig-V-like domain in J1 embryonic stem (ES) cells. ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Cd86^tm1Shr allele

004762

NOD.129S4-Cd86tm1Shr/JbsJ

View Strains carrying   Cd86^tm1Shr     (1 strain)

Strains carrying other alleles of Cd86

003610	B6.129S4-Cd80tm1Shr Cd86tm2Shr/J
005273	NOD.Cg-Rag1tm1Mom Cd86tm2Shr Cd80tm1Shr/JbsJ

View Strains carrying other alleles of Cd86     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Cd86^tm1Shr/Cd86^tm1Shr

        NOD.129S4-Cd86^tm1Shr

• behavior/neurological phenotype
• hindlimb paralysis (MGI Ref ID J:71352)
  • by 20 weeks of age mice start to display a symmetrical mild hind leg paralysis that progresses to a generalized limb paralysis; by 32 weeks of age all female and 30% of male mutant mice display this with the majority of affected mice showing difficulty in walking; this phenotype is not seen when Cd86 nulls are crossed to C57BL/6 or 129/Sv nonautoimmune backgrounds
• immune system phenotype
• decreased T cell proliferation (MGI Ref ID J:93421)
  • transplanted diabetogenic T cells from Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi mice divided primarily in the pancreatic lymph nodes of NOD mice whereas, transferred T cells show reduced proliferation Cd86-deficient NOD mice
  • depletion of Tregs in Cd86-deficient mice partially restores proliferation of Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi T cells in pancreatic lymph nodes
• decreased regulatory T cell number (MGI Ref ID J:93421)
  • in Cd86-deficient mice, numbers of regulatory T cells (Tregs) ie. CD4+CD25+Cd62L^hi, are reduced slightly in the spleen compared to control NOD mice
• decreased susceptibility to autoimmune diabetes (MGI Ref ID J:71352)
  • no female or male mutants on the NOD background developed diabetes compared to 70% and 30% respectively in wild-type Cd86 NOD mice
• increased susceptibility to autoimmune diabetes (MGI Ref ID J:93421)
  • when CD80 expression is blocked, 2-4-week old mice become diabetic, with 90% developing diabetes by 18 weeks; untreated mice are protected from diabetes
• nervous system phenotype
• abnormal action potential (MGI Ref ID J:71352)
  • a dipersion of compound muscle action potentials is observed
• abnormal nerve conduction (MGI Ref ID J:71352)
  • in the sciatic nerve, prolongation of distal latencies and a slowing of conduction velocity is seen with respect to wild-type NOD mice, with conduction block observed in severe cases
• abnormal nervous system morphology (MGI Ref ID J:71352)
  • nulls display severe inflammation in the peripheral nervous system
• abnormal dorsal root ganglion morphology (MGI Ref ID J:71352)
  • mice show mononuclear, cellular infiltrate composed of dendritic cells and scattered CD4+ and CD8+ cells
• abnormal dorsal spinal root morphology (MGI Ref ID J:71352)
  • mice show mononuclear infiltrate in this structure
• abnormal myelin sheath morphology (MGI Ref ID J:71352)
  • some sciatic nerve fibers display increased numbers of Nodes of Ranvier with irregular spacing and irregular myelin sheet thickness
• abnormal ventral spinal root morphology (MGI Ref ID J:71352)
  • mice show mononuclear infiltrate in this structure
• demyelination (MGI Ref ID J:71352)
  • sciatic nerves show electrophysiological indications of a predominantly demyelinating neuropathy
• muscle phenotype
• muscular atrophy (MGI Ref ID J:71352)
  • skeletal muscles show severe focal neurogenic atrophy in severely affected animals, but there are no detectable lesions in the brain or spinal cord
• hematopoietic system phenotype
• decreased T cell proliferation (MGI Ref ID J:93421)
  • transplanted diabetogenic T cells from Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi mice divided primarily in the pancreatic lymph nodes of NOD mice whereas, transferred T cells show reduced proliferation Cd86-deficient NOD mice
  • depletion of Tregs in Cd86-deficient mice partially restores proliferation of Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi T cells in pancreatic lymph nodes
• decreased regulatory T cell number (MGI Ref ID J:93421)
  • in Cd86-deficient mice, numbers of regulatory T cells (Tregs) ie. CD4+CD25+Cd62L^hi, are reduced slightly in the spleen compared to control NOD mice

Cd86^tm1Shr/Cd86^tm1Shr

        involves: 129S4/SvJae

• immune system phenotype
• abnormal humoral immune response (MGI Ref ID J:39089)
  • when immunized with trinitrophenyl conjugates of keyhole limpet hemocyanin or ovalbumin, mice produce reduced levels of antibodies compared to wild-type
• decreased IgG level (MGI Ref ID J:39089)
  • mice produce less than 5% of wild-type levels of IgG1 and IgG2a when immunized with keyhole limpet hemocyanin or ovalbumin conjugates
• absent spleen germinal center (MGI Ref ID J:39089)
  • there is an absence of germinal center formation in mutants
• hematopoietic system phenotype
• absent spleen germinal center (MGI Ref ID J:39089)
  • there is an absence of germinal center formation in mutants

View Research Applications

Research Applications

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

Cd86^tm1Shr related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency Associated with Other Defects
Intracellular Signaling Molecules
Lymphoid Tissue Defects

Internal/Organ Research
Lymphoid Tissue Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cd86tm1Shr
Allele Name		targeted mutation 1, Arlene H Sharpe
Allele Type		Targeted (knock-out)
Common Name(s)		B7-2-; B7.2 KO;
Mutation Made By		Arlene Sharpe,   Brigham and Women's Hospital
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Cd86, CD86 antigen
Chromosome		16
Gene Common Name(s)		B7-2; B7.2; B70; CD28 antigen ligand; CD28LG2; Cd28l2; LAB72; Ly-58; Ly58; MB7-2; MGC34413; lymphocyte antigen 58;
Molecular Note		A neomycin selection cassette replaced an exon encoding the IgV-like domain of the protein and flanking genomic sequences. FACS analysis on splenocytes and LPS-stimulated B cells derived from homozygous mice confirmed that no functional protein was encoded by this allele. [MGI Ref ID J:39089]

Genotyping

Genotyping Information

Genotyping Protocols

Cd86^tm1Shr, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Borriello F; Sethna MP; Boyd SD; Schweitzer AN; Tivol EA; Jacoby D ; Strom TB ; Simpson EM ; Freeman GJ ; Sharpe AH. 1997. B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity 6(3):303-13. [PubMed: 9075931]  [MGI Ref ID J:39089]

Additional References

Pentcheva-Hoang T; Egen JG; Wojnoonski K; Allison JP. 2004. B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity 21(3):401-13. [PubMed: 15357951]  [MGI Ref ID J:93925]

Cd86^tm1Shr related

Ait-Oufella H; Salomon BL; Potteaux S; Robertson AK; Gourdy P; Zoll J; Merval R; Esposito B; Cohen JL; Fisson S; Flavell RA; Hansson GK; Klatzmann D; Tedgui A; Mallat Z. 2006. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12(2):178-80. [PubMed: 16462800]  [MGI Ref ID J:105800]

Bour-Jordan H; Salomon BL; Thompson HL; Szot GL; Bernhard MR; Bluestone JA. 2004. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J Clin Invest 114(7):979-87. [PubMed: 15467837]  [MGI Ref ID J:93421]

Bour-Jordan H; Thompson HL; Bluestone JA. 2005. Distinct effector mechanisms in the development of autoimmune neuropathy versus diabetes in nonobese diabetic mice. J Immunol 175(9):5649-55. [PubMed: 16237054]  [MGI Ref ID J:119359]

Buhlmann JE; Elkin SK; Sharpe AH. 2003. A Role for the B7-1/B7-2:CD28/CTLA-4 Pathway During Negative Selection. J Immunol 170(11):5421-8. [PubMed: 12759417]  [MGI Ref ID J:83454]

Chang TT; Jabs C; Sobel RA; Kuchroo VK; Sharpe AH. 1999. Studies in B7-deficient mice reveal a critical role for B7 costimulation in both induction and effector phases of experimental autoimmune encephalomyelitis. J Exp Med 190(5):733-40. [PubMed: 10477557]  [MGI Ref ID J:57613]

Chung Y; Nurieva R; Esashi E; Wang YH; Zhou D; Gapin L; Dong C. 2008. A critical role of costimulation during intrathymic development of invariant NK T cells. J Immunol 180(4):2276-83. [PubMed: 18250436]  [MGI Ref ID J:131999]

Duan B; Niu H; Xu Z; Sharpe AH; Croker BP; Sobel ES; Morel L. 2008. Intrafollicular location of marginal zone/CD1d(hi) B cells is associated with autoimmune pathology in a mouse model of lupus. Lab Invest 88(9):1008-20. [PubMed: 18607347]  [MGI Ref ID J:138314]

Garcia CA; Martin M; Michalek SM. 2004. Role of B7 costimulatory molecules in mediating systemic and mucosal antibody responses to attenuated Salmonella enterica serovar Typhimurium and its cloned antigen. Infect Immun 72(10):5824-31. [PubMed: 15385483]  [MGI Ref ID J:93124]

Girvin AM; Dal Canto MC; Rhee L; Salomon B; Sharpe A; Bluestone JA; Miller SD. 2000. A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: a comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade. J Immunol 164(1):136-43. [PubMed: 10605004]  [MGI Ref ID J:109892]

Greenwald RJ; Oosterwegel MA; van Der Woude D; Kubal A; Mandelbrot DA; Boussiotis VA; Sharpe AH. 2002. CTLA-4 regulates cell cycle progression during a primary immune response. Eur J Immunol 32(2):366-73. [PubMed: 11807776]  [MGI Ref ID J:74753]

Greenwald RJ; Urban JF; Ekkens MJ; Chen S; Nguyen D; Fang H; Finkelman FD; Sharpe AH; Gause WC. 1999. B7-2 is required for the progression but not the initiation of the type 2 immune response to a gastrointestinal nematode parasite. J Immunol 162(7):4133-9. [PubMed: 10201938]  [MGI Ref ID J:119772]

Hagen KA; Moses CT; Drasler EF; Podetz-Pedersen KM; Jameson SC; Khoruts A. 2004. A role for CD28 in lymphopenia-induced proliferation of CD4 T cells. J Immunol 173(6):3909-15. [PubMed: 15356139]  [MGI Ref ID J:92743]

Hosiawa KA; Wang H; DeVries ME; Garcia B; Liu W; Zhou D; Akram A; Jiang J; Sun H; Cameron MJ; Zhong R; Kelvin DJ. 2005. CD80/CD86 costimulation regulates acute vascular rejection. J Immunol 175(9):6197-204. [PubMed: 16237117]  [MGI Ref ID J:119363]

Kasprowicz DJ; Kohm AP; Berton MT; Chruscinski AJ; Sharpe A; Sanders VM. 2000. Stimulation of the B cell receptor, CD86 (B7-2), and the beta 2-adrenergic receptor intrinsically modulates the level of IgG1 and IgE produced per B cell. J Immunol 165(2):680-90. [PubMed: 10878340]  [MGI Ref ID J:120527]

Kin NW; Sanders VM. 2006. CD86 stimulation on a B cell activates the phosphatidylinositol 3-kinase/Akt and phospholipase C gamma 2/protein kinase C alpha beta signaling pathways. J Immunol 176(11):6727-35. [PubMed: 16709832]  [MGI Ref ID J:131798]

Liang B; Gee RJ; Kashgarian MJ; Sharpe AH; Mamula MJ. 1999. B7 costimulation in the development of lupus: autoimmunity arises either in the absence of B7.1/B7.2 or in the presence of anti-b7.1/B7.2 blocking antibodies. J Immunol 163(4):2322-9. [PubMed: 10438978]  [MGI Ref ID J:118772]

Liang B; Kashgarian MJ; Sharpe AH; Mamula MJ. 2000. Autoantibody responses and pathology regulated by B7-1 and B7-2 costimulation in MRL/lpr lupus J Immunol 165(6):3436-43. [PubMed: 10975864]  [MGI Ref ID J:64568]

Litzinger MT; Su Y; Lei TC; Soukhareva N; Scott DW. 2005. Mechanisms of gene therapy for tolerance: B7 signaling is required for peptide-IgG gene-transferred tolerance induction. J Immunol 175(2):780-7. [PubMed: 16002674]  [MGI Ref ID J:100709]

Mandelbrot DA; Oosterwegel MA; Shimizu K; Yamada A; Freeman GJ; Mitchell RN; Sayegh MH; Sharpe AH. 2001. B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4. J Clin Invest 107(7):881-7. [PubMed: 11285307]  [MGI Ref ID J:68642]

Mark DA; Donovan CE; De Sanctis GT; He HZ; Cernadas M; Kobzik L; Perkins DL; Sharpe A; Finn PW. 2000. B7-1 (CD80) and B7-2 (CD86) have complementary roles in mediating allergic pulmonary inflammation and airway hyperresponsiveness. Am J Respir Cell Mol Biol 22(3):265-71. [PubMed: 10696062]  [MGI Ref ID J:114244]

Matlack R; Yeh K; Rosini L; Gonzalez D; Taylor J; Silberman D; Pennello A; Riggs J. 2006. Peritoneal macrophages suppress T-cell activation by amino acid catabolism. Immunology 117(3):386-95. [PubMed: 16476058]  [MGI Ref ID J:107076]

McAdam AJ; Farkash EA; Gewurz BE; Sharpe AH. 2000. B7 costimulation is critical for antibody class switching and CD8(+) cytotoxic T-lymphocyte generation in the host response to vesicular stomatitis virus. J Virol 74(1):203-8. [PubMed: 10590107]  [MGI Ref ID J:125985]

Mencacci A; Montagnoli C; Bacci A; Cenci E; Pitzurra L; Spreca A; Kopf M; Sharpe AH; Romani L. 2002. CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis. J Immunol 169(6):3180-90. [PubMed: 12218136]  [MGI Ref ID J:120204]

Mizoguchi E; Mizoguchi A; Preffer FI; Bhan AK. 2000. Regulatory role of mature B cells in a murine model of inflammatory bowel disease. Int Immunol 12(5):597-605. [PubMed: 10784605]  [MGI Ref ID J:110524]

Montagnoli C; Bacci A; Bozza S; Gaziano R; Mosci P; Sharpe AH; Romani L. 2002. B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans. J Immunol 169(11):6298-308. [PubMed: 12444136]  [MGI Ref ID J:118777]

Montagnoli C; Fallarino F; Gaziano R; Bozza S; Bellocchio S; Zelante T; Kurup WP; Pitzurra L; Puccetti P; Romani L. 2006. Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J Immunol 176(3):1712-23. [PubMed: 16424201]  [MGI Ref ID J:126452]

Nurieva R; Thomas S; Nguyen T; Martin-Orozco N; Wang Y; Kaja MK; Yu XZ; Dong C. 2006. T-cell tolerance or function is determined by combinatorial costimulatory signals. EMBO J 25(11):2623-33. [PubMed: 16724117]  [MGI Ref ID J:109521]

Odobasic D; Kitching AR; Tipping PG; Holdsworth SR. 2005. CD80 and CD86 costimulatory molecules regulate crescentic glomerulonephritis by different mechanisms. Kidney Int 68(2):584-94. [PubMed: 16014035]  [MGI Ref ID J:114308]

Poussin MA; Tuzun E; Goluszko E; Scott BG; Yang H; Franco JU; Christadoss P. 2003. B7-1 costimulatory molecule is critical for the development of experimental autoimmune myasthenia gravis. J Immunol 170(8):4389-96. [PubMed: 12682276]  [MGI Ref ID J:125435]

Salomon B; Rhee L; Bour-Jordan H; Hsin H; Montag A; Soliven B; Arcella J; Girvin AM; Miller SD; Bluestone JA. 2001. Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice. J Exp Med 194(5):677-84. [PubMed: 11535635]  [MGI Ref ID J:71352]

Santra S; Barouch DH; Jackson SS; Kuroda MJ; Schmitz JE; Lifton MA; Sharpe AH; Letvin NL. 2000. Functional equivalency of B7-1 and B7-2 for costimulating plasmid DNA vaccine-elicited CTL responses J Immunol 165(12):6791-5. [PubMed: 11120800]  [MGI Ref ID J:66171]

Segura E; Nicco C; Lombard B; Veron P; Raposo G; Batteux F; Amigorena S; Thery C. 2005. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood 106(1):216-23. [PubMed: 15790784]  [MGI Ref ID J:107454]

Shin T; Kennedy G; Gorski K; Tsuchiya H; Koseki H; Azuma M; Yagita H; Chen L; Powell J; Pardoll D; Housseau F. 2003. Cooperative B7-1/2 (CD80/CD86) and B7-DC Costimulation of CD4+ T Cells Independent of the PD-1 Receptor. J Exp Med 198(1):31-8. [PubMed: 12847135]  [MGI Ref ID J:84457]

Sugita S; Keino H; Futagami Y; Takase H; Mochizuki M; Stein-Streilein J; Streilein JW. 2006. B7+ iris pigment epithelial cells convert T cells into CTLA-4+, B7-expressing CD8+ regulatory T cells. Invest Ophthalmol Vis Sci 47(12):5376-84. [PubMed: 17122127]  [MGI Ref ID J:123098]

Sugita S; Ng TF; Schwartzkopff J; Streilein JW. 2004. CTLA-4+CD8+ T cells that encounter B7-2+ iris pigment epithelial cells express their own B7-2 to achieve global suppression of T cell activation. J Immunol 172(7):4184-94. [PubMed: 15034031]  [MGI Ref ID J:88713]

Sugita S; Streilein JW. 2003. Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4. J Exp Med 198(1):161-71. [PubMed: 12835481]  [MGI Ref ID J:84466]

Vacchio MS; Williams JA; Hodes RJ. 2005. A novel role for CD28 in thymic selection: elimination of CD28/B7 interactions increases positive selection. Eur J Immunol 35(2):418-27. [PubMed: 15657954]  [MGI Ref ID J:95546]

Yadav D; Judkowski V; Flodstrom-Tullberg M; Sterling L; Redmond WL; Sherman L; Sarvetnick N. 2004. B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets. J Immunol 173(6):3631-9. [PubMed: 15356107]  [MGI Ref ID J:92756]

Zhang P; Martin M; Yang QB; Michalek SM; Katz J. 2004. Role of B7 costimulatory molecules in immune responses and T-helper cell differentiation in response to recombinant HagB from Porphyromonas gingivalis. Infect Immun 72(2):637-44. [PubMed: 14742503]  [MGI Ref ID J:87827]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6/129S4 background. It was backcrossed to B6 for ten generations and has been maintained with intercrosses since N10. It is maintained as a homozygote. Coat color expected from breeding:Black
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
	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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For 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.”

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