Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?+N1p (23-OCT-05) Generation Definitions   Donating Investigator Tullia Lindsten,   Memorial Sloan Kettering Cancer Center

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)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Bak1^tm1Thsn/Bak1^tm1Thsn

        B6.129-Bak1^tm1Thsn

• hematopoietic system phenotype
• abnormal platelet physiology
  • platelet half-life is significantly increased by about 50% compared to controls   (MGI Ref ID J:149205)
• increased platelet cell number
  • platelet cell numbers are about 50% higher than controls   (MGI Ref ID J:149205)
• homeostasis/metabolism phenotype
• abnormal platelet physiology
  • platelet half-life is significantly increased by about 50% compared to controls   (MGI Ref ID J:149205)

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

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

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

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

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

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

• mortality/aging
• partial neonatal lethality
  • majority die within 48 hours of birth, although some survive to adulthood   (MGI Ref ID J:66872)
• limbs/digits/tail phenotype
• interdigital webbing
  • mutants retain interdigital webs on both fore and rear paws   (MGI Ref ID J:66872)
• reproductive system phenotype
• vagina atresia
  • seen in all adult females   (MGI Ref ID J:66872)
• behavior/neurological phenotype
• circling
  • display circling behavior when exposed to external stress   (MGI Ref ID J:66872)
• seizures
  • stress-induced seizure activity   (MGI Ref ID J:66872)
• hearing/vestibular/ear phenotype
• abnormal hearing physiology
  • unresponsive to auditory stimuli   (MGI Ref ID J:66872)
• hematopoietic system phenotype
• abnormal hematopoiesis
  • hematopoietic colony assays show an increase in the number of myeloid colony forming units and a mild increase in erythroid and megakaryocyte colony forming units   (MGI Ref ID J:66872)
• • abnormal B cell morphology
    • B220+ B cells present in the lymph node and spleen are skewed toward a B220^brightIgD- phenotype, indicating an increase in the number of class-switched or memory B cells   (MGI Ref ID J:66872)
  • abnormal T cell morphology
    • T cells that accumulate in mutants are skewed toward a memory cell phenotype   (MGI Ref ID J:66872)
  • anemia
    • mild anemia   (MGI Ref ID J:66872)
  • decreased platelet cell number   (MGI Ref ID J:66872)
  • increased leukocyte cell number   (MGI Ref ID J:66872)
  • • increased lymphocyte cell number
      • increases within the circulation and the peripheral lymphoid organs   (MGI Ref ID J:66872)
      • lymphocytic infiltration is seen in parenchymal organs, liver, and kidney   (MGI Ref ID J:66872)
• abnormal splenocyte physiology
  • isolated splenocytes cultured in suspension show enhanced survival   (MGI Ref ID J:66872)
• enlarged spleen   (MGI Ref ID J:66872)
• increased spleen red pulp amount
  • expanded red pulp contains a large increase in the number of plasma cells and histiocytes   (MGI Ref ID J:66872)
• increased spleen white pulp amount
  • pronounced hyperplasia   (MGI Ref ID J:66872)
• immune system phenotype
• abnormal B cell morphology
  • B220+ B cells present in the lymph node and spleen are skewed toward a B220^brightIgD- phenotype, indicating an increase in the number of class-switched or memory B cells   (MGI Ref ID J:66872)
• abnormal T cell morphology
  • T cells that accumulate in mutants are skewed toward a memory cell phenotype   (MGI Ref ID J:66872)
• abnormal splenocyte physiology
  • isolated splenocytes cultured in suspension show enhanced survival   (MGI Ref ID J:66872)
• enlarged lymph nodes   (MGI Ref ID J:66872)
• enlarged spleen   (MGI Ref ID J:66872)
• increased leukocyte cell number   (MGI Ref ID J:66872)
• • increased lymphocyte cell number
    • increases within the circulation and the peripheral lymphoid organs   (MGI Ref ID J:66872)
    • lymphocytic infiltration is seen in parenchymal organs, liver, and kidney   (MGI Ref ID J:66872)
• increased spleen red pulp amount
  • expanded red pulp contains a large increase in the number of plasma cells and histiocytes   (MGI Ref ID J:66872)
• increased spleen white pulp amount
  • pronounced hyperplasia   (MGI Ref ID J:66872)
• nervous system phenotype
• abnormal brain morphology
  • increase in the number of neurons in multiple regions of the brain   (MGI Ref ID J:66872)
  • large accumulation of small neuronal cells (neural stem cells) with dense chromatin staining in the periventricular region   (MGI Ref ID J:66872)
• • increased brain size   (MGI Ref ID J:66872)
• increased neuron number
  • in multiple regions of the brain   (MGI Ref ID J:66872)
• seizures
  • stress-induced seizure activity   (MGI Ref ID J:66872)
• cellular phenotype
• decreased cellular sensitivity to gamma-irradiation
  • thymocytes show enhanced survival compared to wild-type when exposed to gamma irradiation   (MGI Ref ID J:66872)
• homeostasis/metabolism phenotype
• decreased physiological sensitivity to xenobiotic
  • thymocytes are resistant to treatment with etoposide, a chemotherapeutic agent that normally induces cell death   (MGI Ref ID J:66872)

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 provided by MGI

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,   Memorial Sloan Kettering Cancer Center
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; 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, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Biswas S; Shi Q; Matise L; Cleveland S; Dave U; Zinkel S. 2010. A role for proapoptotic Bax and Bak in T-cell differentiation and transformation. Blood 116(24):5237-46. [PubMed: 20813900]  [MGI Ref ID J:167419]

Campbell S; Hazes B; Kvansakul M; Colman P; Barry M. 2010. Vaccinia virus F1L interacts with Bak using highly divergent Bcl-2 homology domains and replaces the function of Mcl-1. J Biol Chem 285(7):4695-708. [PubMed: 19955184]  [MGI Ref ID J:160040]

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]

Chen M; Felix K; Wang J. 2011. Immune regulation through mitochondrion-dependent dendritic cell death induced by T regulatory cells. J Immunol 187(11):5684-92. [PubMed: 22031758]  [MGI Ref ID J:179762]

Cleland MM; Norris KL; Karbowski M; Wang C; Suen DF; Jiao S; George NM; Luo X; Li Z; Youle RJ. 2011. Bcl-2 family interaction with the mitochondrial morphogenesis machinery. Cell Death Differ 18(2):235-47. [PubMed: 20671748]  [MGI Ref ID J:186336]

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]

Dowling MR; Josefsson EC; Henley KJ; Hodgkin PD; Kile BT. 2010. Platelet senescence is regulated by an internal timer, not damage inflicted by hits. Blood 116(10):1776-8. [PubMed: 20530288]  [MGI Ref ID J:164520]

Duckworth CA; Pritchard DM. 2009. Suppression of apoptosis, crypt hyperplasia, and altered differentiation in the colonic epithelia of bak-null mice. Gastroenterology 136(3):943-52. [PubMed: 19185578]  [MGI Ref ID J:146852]

Dunkle A; Dzhagalov I; He YW. 2010. Mcl-1 promotes survival of thymocytes by inhibition of Bak in a pathway separate from Bcl-2. Cell Death Differ 17(6):994-1002. [PubMed: 20057504]  [MGI Ref ID J:186374]

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]

Fioramonti X; Marsollier N; Song Z; Fakira KA; Patel RM; Brown S; Duparc T; Pica-Mendez A; Sanders NM; Knauf C; Valet P; McCrimmon RJ; Beuve A; Magnan C; Routh VH. 2010. Ventromedial hypothalamic nitric oxide production is necessary for hypoglycemia detection and counterregulation. Diabetes 59(2):519-28. [PubMed: 19934009]  [MGI Ref ID J:164156]

Fontanini A; Foti C; Potu H; Crivellato E; Maestro R; Bernardi P; Demarchi F; Brancolini C. 2009. The Isopeptidase Inhibitor G5 Triggers a Caspase-independent Necrotic Death in Cells Resistant to Apoptosis: A COMPARATIVE STUDY WITH THE PROTEASOME INHIBITOR BORTEZOMIB. J Biol Chem 284(13):8369-81. [PubMed: 19139105]  [MGI Ref ID J:148618]

Gray DH; Kupresanin F; Berzins SP; Herold MJ; O'Reilly LA; Bouillet P; Strasser A. 2012. The BH3-Only Proteins Bim and Puma Cooperate to Impose Deletional Tolerance of Organ-Specific Antigens. Immunity 37(3):451-62. [PubMed: 22960223]  [MGI Ref ID J:187669]

Gruber JJ; Zatechka DS; Sabin LR; Yong J; Lum JJ; Kong M; Zong WX; Zhang Z; Lau CK; Rawlings J; Cherry S; Ihle JN; Dreyfuss G; Thompson CB. 2009. Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell 138(2):328-39. [PubMed: 19632182]  [MGI Ref ID J:152729]

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]

Jabbour AM; Heraud JE; Daunt CP; Kaufmann T; Sandow J; O'Reilly LA; Callus BA; Lopez A; Strasser A; Vaux DL; Ekert PG. 2009. Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim. Cell Death Differ 16(4):555-63. [PubMed: 19079139]  [MGI Ref ID J:158076]

Janssen K; Horn S; Niemann MT; Daniel PT; Schulze-Osthoff K; Fischer U. 2009. Inhibition of the ER Ca2+ pump forces multidrug-resistant cells deficient in Bak and Bax into necrosis. J Cell Sci 122(Pt 24):4481-91. [PubMed: 19920074]  [MGI Ref ID J:155568]

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]

Josefsson EC; James C; Henley KJ; Debrincat MA; Rogers KL; Dowling MR; White MJ; Kruse EA; Lane RM; Ellis S; Nurden P; Mason KD; O'Reilly LA; Roberts AW; Metcalf D; Huang DC; Kile BT. 2011. Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. J Exp Med 208(10):2017-31. [PubMed: 21911424]  [MGI Ref ID J:177288]

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]

Kawai K; Itoh T; Itoh A; Horiuchi M; Wakayama K; Bannerman P; Garbern JY; Pleasure D; Lindsten T. 2009. Maintenance of the relative proportion of oligodendrocytes to axons even in the absence of BAX and BAK. Eur J Neurosci 30(11):2030-41. [PubMed: 20128842]  [MGI Ref ID J:157612]

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]

Kirsch DG; Santiago PM; di Tomaso E; Sullivan JM; Hou WS; Dayton T; Jeffords LB; Sodha P; Mercer KL; Cohen R; Takeuchi O; Korsmeyer SJ; Bronson RT; Kim CF; Haigis KM; Jain RK; Jacks T. 2010. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science 327(5965):593-6. [PubMed: 20019247]  [MGI Ref ID J:156707]

Kodama T; Takehara T; Hikita H; Shimizu S; Shigekawa M; Li W; Miyagi T; Hosui A; Tatsumi T; Ishida H; Kanto T; Hiramatsu N; Yin XM; Hayashi N. 2011. BH3-only Activator Proteins Bid and Bim Are Dispensable for Bak/Bax-dependent Thrombocyte Apoptosis Induced by Bcl-xL Deficiency: MOLECULAR REQUISITES FOR THE MITOCHONDRIAL PATHWAY TO APOPTOSIS IN PLATELETS. J Biol Chem 286(16):13905-13. [PubMed: 21367852]  [MGI Ref ID J:171123]

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]

Lu MY; Liao F. 2011. Interferon-stimulated gene ISG12b2 is localized to the inner mitochondrial membrane and mediates virus-induced cell death. Cell Death Differ 18(6):925-36. [PubMed: 21151029]  [MGI Ref ID J:186970]

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]

Mason KD; Carpinelli MR; Fletcher JI; Collinge JE; Hilton AA; Ellis S; Kelly PN; Ekert PG; Metcalf D; Roberts AW; Huang DC; Kile BT. 2007. Programmed anuclear cell death delimits platelet life span. Cell 128(6):1173-86. [PubMed: 17382885]  [MGI Ref ID J:149205]

Mason KD; Lin A; Robb L; Josefsson EC; Henley KJ; Gray DH; Kile BT; Roberts AW; Strasser A; Huang DC; Waring P; O'Reilly LA. 2013. Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease. Proc Natl Acad Sci U S A 110(7):2599-604. [PubMed: 23349374]  [MGI Ref ID J:194331]

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]

Merino D; Khaw SL; Glaser SP; Anderson DJ; Belmont LD; Wong C; Yue P; Robati M; Phipson B; Fairlie WD; Lee EF; Campbell KJ; Vandenberg CJ; Cory S; Roberts AW; Ludlam MJ; Huang DC; Bouillet P. 2012. Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. Blood 119(24):5807-16. [PubMed: 22538851]  [MGI Ref ID J:188645]

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]

Owens TW; Foster FM; Valentijn A; Gilmore AP; Streuli CH. 2010. Role for X-linked Inhibitor of apoptosis protein upstream of mitochondrial permeabilization. J Biol Chem 285(2):1081-8. [PubMed: 19875445]  [MGI Ref ID J:161686]

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]

Ren D; Tu HC; Kim H; Wang GX; Bean GR; Takeuchi O; Jeffers JR; Zambetti GP; Hsieh JJ; Cheng EH. 2010. BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science 330(6009):1390-3. [PubMed: 21127253]  [MGI Ref ID J:167307]

Reyes NA; Fisher JK; Austgen K; VandenBerg S; Huang EJ; Oakes SA. 2010. Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis. J Clin Invest 120(10):3673-9. [PubMed: 20890041]  [MGI Ref ID J:165330]

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]

Schoenwaelder SM; Yuan Y; Josefsson EC; White MJ; Yao Y; Mason KD; O'Reilly LA; Henley KJ; Ono A; Hsiao S; Willcox A; Roberts AW; Huang DC; Salem HH; Kile BT; Jackson SP. 2009. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood 114(3):663-6. [PubMed: 19387006]  [MGI Ref ID J:150769]

Schweers RL; Zhang J; Randall MS; Loyd MR; Li W; Dorsey FC; Kundu M; Opferman JT; Cleveland JL; Miller JL; Ney PA. 2007. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A 104(49):19500-5. [PubMed: 18048346]  [MGI Ref ID J:141545]

Someya S; Xu J; Kondo K; Ding D; Salvi RJ; Yamasoba T; Rabinovitch PS; Weindruch R; Leeuwenburgh C; Tanokura M; Prolla TA. 2009. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proc Natl Acad Sci U S A 106(46):19432-7. [PubMed: 19901338]  [MGI Ref ID J:154747]

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]

Tormo D; Checinska A; Alonso-Curbelo D; Perez-Guijarro E; Canon E; Riveiro-Falkenbach E; Calvo TG; Larribere L; Megias D; Mulero F; Piris MA; Dash R; Barral PM; Rodriguez-Peralto JL; Ortiz-Romero P; Tuting T; Fisher PB; Soengas MS. 2009. Targeted activation of innate immunity for therapeutic induction of autophagy and apoptosis in melanoma cells. Cancer Cell 16(2):103-14. [PubMed: 19647221]  [MGI Ref ID J:151975]

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]

Vince JE; Wong WW; Gentle I; Lawlor KE; Allam R; O'Reilly L; Mason K; Gross O; Ma S; Guarda G; Anderton H; Castillo R; Hacker G; Silke J; Tschopp J. 2012. Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation. Immunity 36(2):215-27. [PubMed: 22365665]  [MGI Ref ID J:181625]

Wang X; Eno CO; Altman BJ; Zhu Y; Zhao G; Olberding KE; Rathmell JC; Li C. 2011. ER stress modulates cellular metabolism. Biochem J 435(1):285-96. [PubMed: 21241252]  [MGI Ref ID J:170628]

Warr MR; Binnewies M; Flach J; Reynaud D; Garg T; Malhotra R; Debnath J; Passegue E. 2013. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature 494(7437):323-7. [PubMed: 23389440]  [MGI Ref ID J:194535]

Whelan RS; Konstantinidis K; Wei AC; Chen Y; Reyna DE; Jha S; Yang Y; Calvert JW; Lindsten T; Thompson CB; Crow MT; Gavathiotis E; Dorn GW 2nd; O'Rourke B; Kitsis RN. 2012. Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci U S A 109(17):6566-71. [PubMed: 22493254]  [MGI Ref ID J:183839]

White MJ; Schoenwaelder SM; Josefsson EC; Jarman KE; Henley KJ; James C; Debrincat MA; Jackson SP; Huang DC; Kile BT. 2012. Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function. Blood 119(18):4283-90. [PubMed: 22294729]  [MGI Ref ID J:185011]

Wolpaw AJ; Shimada K; Skouta R; Welsch ME; Akavia UD; Pe'er D; Shaik F; Bulinski JC; Stockwell BR. 2011. Modulatory profiling identifies mechanisms of small molecule-induced cell death. Proc Natl Acad Sci U S A 108(39):E771-80. [PubMed: 21896738]  [MGI Ref ID J:176584]

Yee KS; Wilkinson S; James J; Ryan KM; Vousden KH. 2009. PUMA- and Bax-induced autophagy contributes to apoptosis. Cell Death Differ 16(8):1135-45. [PubMed: 19300452]  [MGI Ref ID J:164186]

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

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

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.
Diet Information	LabDiet® 5K54

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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 Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON'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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS 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 JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or services by JACKSON.