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 N5+F10 (01-DEC-06)   Donating Investigator Tullia Lindsten,   University of Pennsylvania

Description
Mice that are homozygous null for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. There were no statistically significant differences in apoptotic cell survival assays between the mutant and wild-type.

Used in conjunction with strain B6.129X1-Bax^tm1Sjk (see Stock No. 002994), to generate the double knock-out Bak/Bax, a model for demonstrating severe defects in the regulation of apoptosis during development and tissue homeostasis.

When bred to a strain with loxP sites inserted into one Bax locus and a null allele at the other locus (Stock No. 006329) and a strain with a Cd19 null allele and expressing Cre recombinase during B lymphocyte development and differentiation (Stock No. 004126), this mutant mouse strain may be useful in studies of autoimmune disease.

When bred to a strain with loxP sites inserted into one Bax locus and a null allele at the other locus (Stock No. 006329) and a strain expressing interferon inducible Cre recombinase (Stock No. 003556), this mutant mouse strain may be useful in studies of autoimmune disease.

Development
A targeting vector containing the neomycin resistance gene was used to remove exons III-VI of the Bak1 gene. The construct was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Bak1^tm1Thsn allele

006329

B6;129-Baxtm2Sjk Bak1tm1Thsn/J

View Strains carrying   Bak1^tm1Thsn     (1 strain)

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.

Bak1^tm1Thsn/Bak1^tm1Thsn

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:66872)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Bak1^tm1Thsn/Bak1^tm1Thsn Bax^tm1Sjk/Bax^tm2Sjk Cd19^tm1(cre)Cgn/Cd19⁺

        involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ   (conditional)

• immune system phenotype
• abnormal B cell number (MGI Ref ID J:100463)
• decreased marginal zone B cell number (MGI Ref ID J:100463)
  • relative number of CD21^highCD23^low marginal zone B cells is decreased
• increased B cell number (MGI Ref ID J:100463)
  • increase in the number of B cells at all stages of development in the bone marrow and spleen of transitional B cells, an increase in CD21^intCD23^high follicular B cells and B-2 cells, but not B-1 cells, from the peritoneal cavity
• increased B-2 B cell number (MGI Ref ID J:100463)
  • an increase in B-2 cell number, but not B-1 cells, from the peritoneal cavity
• increased follicular B cell number (MGI Ref ID J:100463)
  • an increase in CD21^intCD23^high follicular B cells
• increased pre-B cell number (MGI Ref ID J:100463)
  • a 4-fold increase in the number of IgM⁺ immature B cells
• increased transitional stage B cell number (MGI Ref ID J:100463)
  • a 3-5 fold increase in the numbers of transitional B cells
• abnormal B cell physiology (MGI Ref ID J:100463)
  • B cells are highly resistant to multiple cell death stimuli, including cytokine withdrawal, BCR crosslinking, steroid treatment, and DNA damage
  • cell cycle progression of splenic B cells is impaired after stimulation with mitogens LPS and anti-IgM, but not CpG-DNA
• increased immunoglobulin level (MGI Ref ID J:100463)
  • all isotypes were 5-10 times higher than controls
• increased IgA level (MGI Ref ID J:100463)
• increased IgG level (MGI Ref ID J:100463)
  • increased IgG1, IgG2, IgG2b and IgG3
• increased IgM level (MGI Ref ID J:100463)
• increased pro-B cell number (MGI Ref ID J:100463)
  • 4-fold increase in the number of CD43⁺IgM^- Pro-B cells
• hematopoietic system phenotype
• abnormal B cell number (MGI Ref ID J:100463)
• decreased marginal zone B cell number (MGI Ref ID J:100463)
  • relative number of CD21^highCD23^low marginal zone B cells is decreased
• increased B cell number (MGI Ref ID J:100463)
  • increase in the number of B cells at all stages of development in the bone marrow and spleen of transitional B cells, an increase in CD21^intCD23^high follicular B cells and B-2 cells, but not B-1 cells, from the peritoneal cavity
• increased B-2 B cell number (MGI Ref ID J:100463)
  • an increase in B-2 cell number, but not B-1 cells, from the peritoneal cavity
• increased follicular B cell number (MGI Ref ID J:100463)
  • an increase in CD21^intCD23^high follicular B cells
• increased pre-B cell number (MGI Ref ID J:100463)
  • a 4-fold increase in the number of IgM⁺ immature B cells
• increased transitional stage B cell number (MGI Ref ID J:100463)
  • a 3-5 fold increase in the numbers of transitional B cells
• increased bone marrow cell number (MGI Ref ID J:100463)
  • 2-fold increase in total cellularity of bone marrow cells, due to accumulation of developing B cells
• increased pro-B cell number (MGI Ref ID J:100463)
  • 4-fold increase in the number of CD43⁺IgM^- Pro-B cells

Bak1^tm1Thsn/Bak1^tm1Thsn Bax^tm1Sjk/Bax^tm2Sjk Tg(Mx1-cre)1Cgn/0

        involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA   (conditional)

• life span-post-weaning/aging
• premature death (MGI Ref ID J:100463)
  • by 35 weeks after induction of Cre expression (and thus Bax deletion) in the adult, 78% of mutants die compared to 5% of wild-type
• immune system phenotype
• abnormal T cell differentiation (MGI Ref ID J:100463)
  • thymic T cell development is perturbed after poly(I:C) injection
• arthritis (MGI Ref ID J:100463)
  • develops after poly(I:C) injection to induce Bax deletion in the adult
• glomerulonephritis (MGI Ref ID J:100463)
  • develops after poly(I:C) injection to induce Bax deletion in the adult
• increased anti-double stranded DNA antibody level (MGI Ref ID J:100463)
  • show elevated serum antinuclear antibodies and anti-dsDNA antibody after 30 weeks of poly(I:C) injection to induce Bax deletion in the adult
• increased leukocyte cell number (MGI Ref ID J:100463)
  • accumulation of white blood cells after injection of poly(I:C) to induce Cre expression in adult
• increased lymphocyte cell number (MGI Ref ID J:100463)
• increased B cell number (MGI Ref ID J:100463)
  • exhibit accumulation of B cells in the spleen and bone marrow 6 weeks after poly(I:C) injection to induce Cre expression
• increased susceptibility to autoimmune disorder (MGI Ref ID J:100463)
  • develop autoimmune disease after poly(I:C) injection to induce Bax deletion in the adult
• hematopoietic system phenotype
• abnormal T cell differentiation (MGI Ref ID J:100463)
  • thymic T cell development is perturbed after poly(I:C) injection
• increased leukocyte cell number (MGI Ref ID J:100463)
  • accumulation of white blood cells after injection of poly(I:C) to induce Cre expression in adult
• increased lymphocyte cell number (MGI Ref ID J:100463)
• increased B cell number (MGI Ref ID J:100463)
  • exhibit accumulation of B cells in the spleen and bone marrow 6 weeks after poly(I:C) injection to induce Cre expression
• renal/urinary system phenotype
• glomerulonephritis (MGI Ref ID J:100463)
  • develops after poly(I:C) injection to induce Bax deletion in the adult
• skeleton phenotype
• arthritis (MGI Ref ID J:100463)
  • develops after poly(I:C) injection to induce Bax deletion in the adult

Bak1^tm1Thsn/Bak1^tm1Thsn Bax^tm1Sjk/Bax^tm1Sjk

        involves: 129S1/Sv * 129S1/SvImJ * 129X1/SvJ * C57BL/6

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:66872)
  • many, but not all, animals died in the perinatal period
• behavior/neurological phenotype
• circling (MGI Ref ID J:66872)
• seizures (MGI Ref ID J:66872)
  • stress-induced seizure activity
• hearing/vestibular/ear phenotype
• abnormal hearing physiology (MGI Ref ID J:66872)
  • unresponsive to auditory stimuli
• circling (MGI Ref ID J:66872)
• hematopoietic system phenotype
• anemia (MGI Ref ID J:66872)
  • mild anemia
• decreased platelet cell number (MGI Ref ID J:66872)
• enlarged spleen (MGI Ref ID J:66872)
• increased leukocyte cell number (MGI Ref ID J:66872)
• immune system phenotype
• enlarged lymph nodes (MGI Ref ID J:66872)
• enlarged spleen (MGI Ref ID J:66872)
• increased leukocyte cell number (MGI Ref ID J:66872)
• limbs/digits/tail phenotype
• interdigital webbing (MGI Ref ID J:66872)
• reproductive system phenotype
• fused vagina opening (MGI Ref ID J:66872)
• nervous system phenotype
• abnormal brain morphology (MGI Ref ID J:66872)
  • increased number of neurons in multiple regions of the brain
• seizures (MGI Ref ID J:66872)
  • stress-induced seizure activity

View Research Applications

Research Applications

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

Bak1^tm1Thsn related

Developmental Biology Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Bak1tm1Thsn
Allele Name		targeted mutation 1, Craig B Thompson
Allele Type		Targeted (knock-out)
Common Name(s)		bak-;
Mutation Made By		Craig Thompson,   University of Pennsylvania
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Bak1, BCL2-antagonist/killer 1
Chromosome		17
Gene Common Name(s)		BAK; BAK-LIKE; BCL2L7; CDN1; MGC108627; MGC117255; MGC3887; N-Bak;
Molecular Note		A neomycin resistance cassette replaced a genomic fragment containing exons 2-6. These exons encode the Bcl-2 homology domains of the encoded protein. Western blot analysis on spleen and thymus lysates derived from homozygous mice confirmed that no detectable protein is expressed from this allele. [MGI Ref ID J:66872]

Genotyping

Genotyping Information

Genotyping Protocols

Bak1^tm1Thsn, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Lindsten T; Ross AJ; King A; Zong WX; Rathmell JC; Shiels HA; Ulrich E; Waymire KG; Mahar P; Frauwirth K; Chen Y; Wei M; Eng VM; Adelman DM; Simon MC; Ma A; Golden JA; Evan G; Korsmeyer SJ; MacGregor GR; Thompson CB. 2000. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 6(6):1389-99. [PubMed: 11163212]  [MGI Ref ID J:66872]

Additional References

Bak1^tm1Thsn related

Akhtar RS; Geng Y; Klocke BJ; Roth KA. 2006. Neural precursor cells possess multiple p53-dependent apoptotic pathways. Cell Death Differ 13(10):1727-39. [PubMed: 16514420]  [MGI Ref ID J:126291]

Baines CP; Kaiser RA; Sheiko T; Craigen WJ; Molkentin JD. 2007. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9(5):550-5. [PubMed: 17417626]  [MGI Ref ID J:129616]

Billen LP; Kokoski CL; Lovell JF; Leber B; Andrews DW. 2008. Bcl-XL inhibits membrane permeabilization by competing with Bax. PLoS Biol 6(6):e147. [PubMed: 18547146]  [MGI Ref ID J:139497]

Chao JR; Parganas E; Boyd K; Hong CY; Opferman JT; Ihle JN. 2008. Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons. Nature 452(7183):98-102. [PubMed: 18288109]  [MGI Ref ID J:132627]

Coultas L; Bouillet P; Loveland KL; Meachem S; Perlman H; Adams JM; Strasser A. 2005. Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis. EMBO J 24(22):3963-73. [PubMed: 16270031]  [MGI Ref ID J:103605]

Dansen TB; Whitfield J; Rostker F; Brown-Swigart L; Evan GI. 2006. Specific requirement for Bax, not Bak, in Myc-induced apoptosis and tumor suppression in vivo. J Biol Chem 281(16):10890-5. [PubMed: 16464852]  [MGI Ref ID J:108676]

Degenhardt K; Sundararajan R; Lindsten T; Thompson C; White E. 2002. Bax and Bak independently promote cytochrome C release from mitochondria. J Biol Chem 277(16):14127-34. [PubMed: 11836241]  [MGI Ref ID J:76058]

Fannjiang Y; Kim CH; Huganir RL; Zou S; Lindsten T; Thompson CB; Mito T; Traystman RJ; Larsen T; Griffin DE; Mandir AS; Dawson TM; Dike S; Sappington AL; Kerr DA; Jonas EA; Kaczmarek LK; Hardwick JM. 2003. BAK alters neuronal excitability and can switch from anti- to pro-death function during postnatal development. Dev Cell 4(4):575-85. [PubMed: 12689595]  [MGI Ref ID J:109013]

Hahn P; Lindsten T; Lyubarsky A; Ying GS; Pugh EN Jr; Thompson CB; Dunaief JL. 2004. Deficiency of Bax and Bak protects photoreceptors from light damage in vivo. Cell Death Differ 11(11):1192-7. [PubMed: 15272317]  [MGI Ref ID J:134629]

Hahn P; Lindsten T; Tolentino M; Thompson CB; Bennett J; Dunaief JL. 2005. Persistent fetal ocular vasculature in mice deficient in bax and bak. Arch Ophthalmol 123(6):797-802. [PubMed: 15955981]  [MGI Ref ID J:115735]

Hetz C; Bernasconi P; Fisher J; Lee AH; Bassik MC; Antonsson B; Brandt GS; Iwakoshi NN; Schinzel A; Glimcher LH; Korsmeyer SJ. 2006. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 312(5773):572-6. [PubMed: 16645094]  [MGI Ref ID J:108337]

Hutcheson J; Perlman H. 2007. Loss of Bim results in abnormal accumulation of mature CD4-CD8-CD44-CD25- thymocytes. Immunobiology 212(8):629-36. [PubMed: 17869640]  [MGI Ref ID J:129934]

Hutcheson J; Scatizzi JC; Bickel E; Brown NJ; Bouillet P; Strasser A; Perlman H. 2005. Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis. J Exp Med 201(12):1949-60. [PubMed: 15967824]  [MGI Ref ID J:99285]

Jones RG; Bui T; White C; Madesh M; Krawczyk CM; Lindsten T; Hawkins BJ; Kubek S; Frauwirth KA; Wang YL; Conway SJ; Roderick HL; Bootman MD; Shen H; Foskett JK; Thompson CB. 2007. The Proapoptotic Factors Bax and Bak Regulate T Cell Proliferation through Control of Endoplasmic Reticulum Ca(2+) Homeostasis. Immunity 27(2):268-80. [PubMed: 17692540]  [MGI Ref ID J:124342]

Karbowski M; Norris KL; Cleland MM; Jeong SY; Youle RJ. 2006. Role of Bax and Bak in mitochondrial morphogenesis. Nature 443(7112):658-62. [PubMed: 17035996]  [MGI Ref ID J:113296]

Kirsch DG; Dinulescu DM; Miller JB; Grimm J; Santiago PM; Young NP; Nielsen GP; Quade BJ; Chaber CJ; Schultz CP; Takeuchi O; Bronson RT; Crowley D; Korsmeyer SJ; Yoon SS; Hornicek FJ; Weissleder R; Jacks T. 2007. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med 13(8):992-7. [PubMed: 17676052]  [MGI Ref ID J:125101]

Konishi A; Shimizu S; Hirota J; Takao T; Fan Y; Matsuoka Y; Zhang L; Yoneda Y; Fujii Y; Skoultchi AI; Tsujimoto Y. 2003. Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. Cell 114(6):673-88. [PubMed: 14505568]  [MGI Ref ID J:107681]

Leu JI; George DL. 2007. Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria. Genes Dev 21(23):3095-109. [PubMed: 18056423]  [MGI Ref ID J:127809]

Lindenboim L; Kringel S; Braun T; Borner C; Stein R. 2005. Bak but not Bax is essential for Bcl-xS-induced apoptosis. Cell Death Differ 12(7):713-23. [PubMed: 15861188]  [MGI Ref ID J:111864]

Lindsten T; Golden JA; Zong WX; Minarcik J; Harris MH; Thompson CB. 2003. The proapoptotic activities of Bax and Bak limit the size of the neural stem cell pool. J Neurosci 23(35):11112-9. [PubMed: 14657169]  [MGI Ref ID J:87971]

Lindsten T; Thompson CB. 2006. Cell death in the absence of Bax and Bak. Cell Death Differ 13(8):1272-6. [PubMed: 16676001]  [MGI Ref ID J:126409]

Lum JJ; Bauer DE; Kong M; Harris MH; Li C; Lindsten T; Thompson CB. 2005. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120(2):237-48. [PubMed: 15680329]  [MGI Ref ID J:97305]

McKenzie MD; Carrington EM; Kaufmann T; Strasser A; Huang DC; Kay TW; Allison J; Thomas HE. 2008. Proapoptotic BH3-only protein Bid is essential for death receptor-induced apoptosis of pancreatic beta-cells. Diabetes 57(5):1284-92. [PubMed: 18252892]  [MGI Ref ID J:135326]

Moubarak RS; Yuste VJ; Artus C; Bouharrour A; Greer PA; Menissier-de Murcia J; Susin SA. 2007. Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis. Mol Cell Biol 27(13):4844-62. [PubMed: 17470554]  [MGI Ref ID J:122803]

Pardo J; Urban C; Galvez EM; Ekert PG; Muller U; Kwon-Chung J; Lobigs M; Mullbacher A; Wallich R; Borner C; Simon MM. 2006. The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice. J Cell Biol 174(4):509-19. [PubMed: 16893972]  [MGI Ref ID J:112620]

Przemeck SM; Duckworth CA; Pritchard DM. 2007. Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2. Am J Physiol Gastrointest Liver Physiol 292(2):G620-7. [PubMed: 17068116]  [MGI Ref ID J:124814]

Ross AJ; Amy SP; Mahar PL; Lindsten T; Knudson CM; Thompson CB; Korsmeyer SJ; MacGregor GR. 2001. BCLW Mediates Survival of Postmitotic Sertoli Cells by Regulating BAX Activity. Dev Biol 239(2):295-308. [PubMed: 11784036]  [MGI Ref ID J:72582]

Ruiz-Vela A; Opferman JT; Cheng EH; Korsmeyer SJ. 2005. Proapoptotic BAX and BAK control multiple initiator caspases. EMBO Rep 6(4):379-85. [PubMed: 15776018]  [MGI Ref ID J:97306]

Takeuchi O; Fisher J; Suh H; Harada H; Malynn BA; Korsmeyer SJ. 2005. Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease. Proc Natl Acad Sci U S A 102(32):11272-7. [PubMed: 16055554]  [MGI Ref ID J:100463]

Upton JP; Austgen K; Nishino M; Coakley KM; Hagen A; Han D; Papa FR; Oakes SA. 2008. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol 28(12):3943-51. [PubMed: 18426910]  [MGI Ref ID J:137299]

Zhu Y; Liu X; Hildeman D; Peyerl FW; White J; Kushnir E; Kappler J; Marrack P. 2006. Bax does not have to adopt its final form to drive T cell death. J Exp Med 203(5):1147-52. [PubMed: 16651384]  [MGI Ref ID J:124139]

Zong WX; Ditsworth D; Bauer DE; Wang ZQ; Thompson CB. 2004. Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev 18(11):1272-82. [PubMed: 15145826]  [MGI Ref ID J:118568]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	Mice arose on a B6;129 background and has been backcrossed to C57Bl/6 for 5 generations before being made homozygous.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K54

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.

Control Information

	Control
	000664 C57BL/6J	(approximate)
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

Contact information

General inquiries

Contracts Administration

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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