Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N13+F12 (29-JUL-08)   Donating Investigator Andreas Strasser,   Walter and Eliza Hall Inst of Med Res

Description
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No full length gene product (protein) is immunodetected in spleen cells from homozygous mutant mice. Homozygous mice have lympho-myeloid hyperplasia and reduced platelet number. Lymphocytes are insensitive to certain apoptotic stimuli. Both homozygous and heterozygous mice exhibit progressive systemic autoimmune disease. This mutant mouse strain may be useful in studies of apoptosis, degenerative and autoimmune diseases, including lupus erythematosus and autoimmune kidney disease.

Development
A targeting vector containing a floxed neomycin resistance gene and a thymidine kinase gene was used to disrupt the exon encoding the BH3 domain. The construct was electroporated into 129S1 derived W9.5 embryonic stem (ES) cells. correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast

        B6.129S1-Bcl2l11^tm1.1Ast

• immune system phenotype
• abnormal B cell morphology (MGI Ref ID J:133084)
• increased immature B cell number (MGI Ref ID J:133084)
• increased transitional stage B cell number (MGI Ref ID J:133084)
  • T1 transitional B cells are insignificantly elevated
  • increased T1 transitional B cells in inguinal lymph nodes
• increased mature B cell number (MGI Ref ID J:133084)
• abnormal NK cell morphology (MGI Ref ID J:123409)
  • following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells
• increased NK cell number (MGI Ref ID J:123409)
  • mice have a higher percent of KLRG1+CD27- NK cells in the spleen, liver and bone marrow compared to wild-type mice
• abnormal lymphocyte physiology (MGI Ref ID J:73316)
  • survival of mature resting T and B cells in the absence of cytokines is improved compared to wild-type cells
• abnormal response to infection (MGI Ref ID J:123409)
  • following infection with mouse cytomegalovirus infection, more NK cell survive at day 10 and 14 than in wild-type mice
• decreased T cell apoptosis (MGI Ref ID J:133084)
  • double positive T cells with increased resistance to the apoptotic effects of dexamethasone
• homeostasis/metabolism phenotype
• decreased sensitivity to xenobiotics (MGI Ref ID J:123409)
  • NK cells are more resistant to LY294002-induced apoptosis
• cellular phenotype
• decreased apoptosis (MGI Ref ID J:123409)
  • NK cells are more resistant to LY294002-induced apoptosis
  • sympathetic neurons are partially protected from apoptosis induced by the withdrawal of nerve growth factor
• nervous system phenotype
• abnormal sympathetic neuron morphology (MGI Ref ID J:124044)
  • sympathetic neurons are partially protected from apoptosis induced by the withdrawal of nerve growth factor
• hematopoietic system phenotype
• abnormal B cell morphology (MGI Ref ID J:133084)
• increased immature B cell number (MGI Ref ID J:133084)
• increased transitional stage B cell number (MGI Ref ID J:133084)
  • T1 transitional B cells are insignificantly elevated
  • increased T1 transitional B cells in inguinal lymph nodes
• increased mature B cell number (MGI Ref ID J:133084)
• abnormal NK cell morphology (MGI Ref ID J:123409)
  • following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells
• increased NK cell number (MGI Ref ID J:123409)
  • mice have a higher percent of KLRG1+CD27- NK cells in the spleen, liver and bone marrow compared to wild-type mice
• decreased T cell apoptosis (MGI Ref ID J:133084)
  • double positive T cells with increased resistance to the apoptotic effects of dexamethasone

Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast

        B6.129-Bcl2l11^tm1.1Ast/J

• hematopoietic system phenotype
• decreased lymphocyte cell number (MGI Ref ID J:137609)
• immune system phenotype
• decreased lymphocyte cell number (MGI Ref ID J:137609)

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

Bcl2l11^tm1.1Ast/Bcl2l11⁺

        involves: 129S1/Sv * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:58641)
  • by 1 year of age 35% of heterozygotes are terminally ill
• immune system phenotype
• abnormal lymphocyte physiology (MGI Ref ID J:58641)
  • pre-T cells cultured without cytokines or with ionomycin or taxol survive better than wild-type cells but not as well as homozygous cells
• increased IgA level (MGI Ref ID J:58641)
  • increased at 6 to 12 months of age but less than in homozygous mice
• increased IgG level (MGI Ref ID J:58641)
  • increased at 6 to 12 months of age but less than in homozygous mice
• increased IgM level (MGI Ref ID J:58641)
  • increased at 6 to 12 months of age but less than in homozygous mice
• glomerulonephritis (MGI Ref ID J:58641)
  • by 1 year of about 85% of terminally ill heterozygotes have immune complex glomerulonephritis
• increased susceptibility to autoimmune disorder (MGI Ref ID J:58641)
  • older heterozygotes develop lymphadenopathy
• vasculitis (MGI Ref ID J:58641)
  • about 20% of terminally ill heterozygotes show signs of vasculitis or cardiac infarction
• renal/urinary system phenotype
• glomerulonephritis (MGI Ref ID J:58641)
  • by 1 year of about 85% of terminally ill heterozygotes have immune complex glomerulonephritis
• cardiovascular system phenotype
• vasculitis (MGI Ref ID J:58641)
  • about 20% of terminally ill heterozygotes show signs of vasculitis or cardiac infarction

Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast

        involves: 129S1/Sv * C57BL/6

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:58641)
  • about half die before E10; however, this percentage is highly variable and background dependent
• life span-post-weaning/aging
• premature death (MGI Ref ID J:58641)
  • by 1 year of age 55% of homozygotes are terminally ill with 85% of these developing kidney disease (immune complex glomerulonephritis)
• immune system phenotype
• abnormal lymphocyte physiology (MGI Ref ID J:58641)
  • pre-T cells cultured without cytokines or with ionomycin or taxol survive 10 to 30 times better than wild-type cells
  • pre-T cells are resistant to dexamethasone or gamma-irradiation induced cell death but not to phorbol 12-myristate 13-acetate (PMA) or Fas ligand induced cell death
  • pre-B cells are also resistant to cell death induced by cytokine withdrawal, ionomycin, taxol, and dexamethasone but display sensitivity to cell death similar to wild-type following gamma irradiation or exposure to PMA or Fas ligand
• increased IgA level (MGI Ref ID J:58641)
  • elevated about 3-fold at 6 to 12 months of age
• increased IgG level (MGI Ref ID J:58641)
  • elevated about 10-fold at 6 to 12 months of age
• increased IgM level (MGI Ref ID J:58641)
  • elevated about 3-fold at 6 to 12 months of age
• abnormal plasma cell morphology (MGI Ref ID J:58641)
  • at 6 to 12 months of age the number of IgM and IgG is increased by about 4-fold and 30- to 200-fold, respectively
• abnormal spleen morphology (MGI Ref ID J:58641)
• abnormal spleen cellularity (MGI Ref ID J:132217)
  • total number of CD19+ splenocytes is higher than wild-type
• abnormal splenic cell ratio (MGI Ref ID J:132217)
  • T1:follicular B cell ratio is higher than wild-type
• spleen hyperplasia (MGI Ref ID J:58641)
  • seen in older homozygotes with plasma cells most severely affected
  • total number of splenocytes is increased relative to wild-type
• enlarged spleen (MGI Ref ID J:58641)
  • in older homozygotes spleen size is increased 5- to 10-fold
• spleen hyperplasia (MGI Ref ID J:58641)
  • seen in older homozygotes with plasma cells most severely affected
  • total number of splenocytes is increased relative to wild-type
• decreased double-positive T cell number (MGI Ref ID J:58641)
  • in adult mice, thymic pre-T cells are reduced by about 50% compared to wild-type; however in newborns thymocyte composition is similar to wild-type
• increased autoantibody level (MGI Ref ID J:132217)
  • total anti-IgM antibody levels are increased compared to wild-type
• increased anti-nuclear antigen antibody level (MGI Ref ID J:132217)
  • anti-nuclear antibodies are increased compared to wild-type
• increased anti-double stranded DNA antibody level (MGI Ref ID J:132217)
  • anti-SsDNA IgM and IgG antibodies are increased compared to wild-type
• increased anti-histone antibody level (MGI Ref ID J:132217)
  • increased compared to wild-type
• increased anti-single stranded DNA antibody level (MGI Ref ID J:132217)
  • anti-ssDNA IgM and IgG antibodies are increased compared to wild-type
• increased inflammatory response (MGI Ref ID J:58641)
• glomerulonephritis (MGI Ref ID J:58641)
  • by 1 year of about 85% of terminally ill homozygotes have immune complex glomerulonephritis
• vasculitis (MGI Ref ID J:58641)
  • about 20% of terminally ill homozygotes show signs of vasculitis or cardiac infarction
• increased leukocyte cell number (MGI Ref ID J:58641)
  • blood, spleen, and lymph node leukocyte numbers are elevated several fold mostly as a result of increased B and T cell counts
  • these cells are mostly small, noncycling cells suggesting an increase in cell survival rather than proliferation
  • however, the number of red cells is normal and the number of hematopoietic progenitor cells in the bone marrow is similar to wild-type
• increased B cell number (MGI Ref ID J:58641)
  • 2- to 4-fold increase
• increased follicular B cell number (MGI Ref ID J:132217)
  • higher in spleen relative to wild-type and Fas^lpr homozygotes
• increased immature B cell number (MGI Ref ID J:132217)
  • plasmablast numbers in spleen are increased relative to wild-type
• increased transitional stage B cell number (MGI Ref ID J:132217)
  • higher numbers of T1 and T2 B cells in spleen relative to wild-type
• increased marginal zone B cell number (MGI Ref ID J:132217)
  • higher in spleen relative to wild-type and Fas^lpr homozygotes
• increased T cell number (MGI Ref ID J:58641)
  • 2- to 4-fold increase involving mostly mature T cells is seen in adult mice
• increased CD4-positive T cell number (MGI Ref ID J:58641)
  • 2- to 3-fold increase in the number of CD4+ T cells is seen in adult mice
• increased CD8-positive T cell number (MGI Ref ID J:58641)
  • 2- to 3-fold increase in the number of CD8+ T cells is seen in adult mice
• increased double-negative T cell number (MGI Ref ID J:58641)
  • 2- to 3-fold increase is seen in adult mice
• increased granulocyte number (MGI Ref ID J:58641)
  • 2- to 4-fold increase
• increased monocyte cell number (MGI Ref ID J:58641)
  • 2- to 4-fold increase
• increased susceptibility to autoimmune disorder (MGI Ref ID J:58641)
  • older homozygotes develop lymphadenopathy
• renal/urinary system phenotype
• abnormal kidney morphology (MGI Ref ID J:132217)
  • number of macrophages surrounding glomeruli is increased compared to wild-type and Fas^lpr homozygotes
  • IgG deposits mainly localized to basement glomerular membrane are increased relative to wild-type
  • number of macrophages surrounding glomeruli is increased compared to wild-type, and is similar to that in double mutants
  • higher numbers of apoptotic cells are detected in glomeruli compared to wild-type
• abnormal renal glomerular capsule (MGI Ref ID J:58641)
  • proliferation of capsular epithelial cells is seen in homozygotes with kidney disease
• abnormal renal glomerulus morphology (MGI Ref ID J:58641)
  • hypercellularity is seen in homozygotes with kidney disease
• glomerulonephritis (MGI Ref ID J:58641)
  • by 1 year of about 85% of terminally ill homozygotes have immune complex glomerulonephritis
• dilated renal tubules (MGI Ref ID J:58641)
  • eosinophilic deposits are seen in dilated renal tubules in homozygotes with kidney disease
• homeostasis/metabolism phenotype
• increased blood urea nitrogen level (MGI Ref ID J:58641)
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:127640)
  • unlike mice homozygous for Bbc3^tm1Ast neuron sensitivity to oxidative stressor induced apoptosis is similar to controls
• hematopoietic system phenotype
• abnormal plasma cell morphology (MGI Ref ID J:58641)
  • at 6 to 12 months of age the number of IgM and IgG is increased by about 4-fold and 30- to 200-fold, respectively
• abnormal spleen morphology (MGI Ref ID J:58641)
• abnormal spleen cellularity (MGI Ref ID J:132217)
  • total number of CD19+ splenocytes is higher than wild-type
• abnormal splenic cell ratio (MGI Ref ID J:132217)
  • T1:follicular B cell ratio is higher than wild-type
• spleen hyperplasia (MGI Ref ID J:58641)
  • seen in older homozygotes with plasma cells most severely affected
  • total number of splenocytes is increased relative to wild-type
• enlarged spleen (MGI Ref ID J:58641)
  • in older homozygotes spleen size is increased 5- to 10-fold
• spleen hyperplasia (MGI Ref ID J:58641)
  • seen in older homozygotes with plasma cells most severely affected
  • total number of splenocytes is increased relative to wild-type
• decreased double-positive T cell number (MGI Ref ID J:58641)
  • in adult mice, thymic pre-T cells are reduced by about 50% compared to wild-type; however in newborns thymocyte composition is similar to wild-type
• decreased platelet cell number (MGI Ref ID J:58641)
  • platelet count is reduced to about 1/2 of wild-type; however, megakaryocyte numbers are normal
• increased leukocyte cell number (MGI Ref ID J:58641)
  • blood, spleen, and lymph node leukocyte numbers are elevated several fold mostly as a result of increased B and T cell counts
  • these cells are mostly small, noncycling cells suggesting an increase in cell survival rather than proliferation
  • however, the number of red cells is normal and the number of hematopoietic progenitor cells in the bone marrow is similar to wild-type
• increased B cell number (MGI Ref ID J:58641)
  • 2- to 4-fold increase
• increased follicular B cell number (MGI Ref ID J:132217)
  • higher in spleen relative to wild-type and Fas^lpr homozygotes
• increased immature B cell number (MGI Ref ID J:132217)
  • plasmablast numbers in spleen are increased relative to wild-type
• increased transitional stage B cell number (MGI Ref ID J:132217)
  • higher numbers of T1 and T2 B cells in spleen relative to wild-type
• increased marginal zone B cell number (MGI Ref ID J:132217)
  • higher in spleen relative to wild-type and Fas^lpr homozygotes
• increased T cell number (MGI Ref ID J:58641)
  • 2- to 4-fold increase involving mostly mature T cells is seen in adult mice
• increased CD4-positive T cell number (MGI Ref ID J:58641)
  • 2- to 3-fold increase in the number of CD4+ T cells is seen in adult mice
• increased CD8-positive T cell number (MGI Ref ID J:58641)
  • 2- to 3-fold increase in the number of CD8+ T cells is seen in adult mice
• increased double-negative T cell number (MGI Ref ID J:58641)
  • 2- to 3-fold increase is seen in adult mice
• increased granulocyte number (MGI Ref ID J:58641)
  • 2- to 4-fold increase
• increased monocyte cell number (MGI Ref ID J:58641)
  • 2- to 4-fold increase
• cardiovascular system phenotype
• vasculitis (MGI Ref ID J:58641)
  • about 20% of terminally ill homozygotes show signs of vasculitis or cardiac infarction

Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast

        involves: 129S1/Sv

• immune system phenotype
• abnormal CD4-positive T cell number (MGI Ref ID J:132819)
  • 2- to 4- fold increase
• abnormal CD8-positive T cell physiology (MGI Ref ID J:132819)
  • HSV-1 antigen specific CD8+ T cells show nearly complete resistance to cytokine withdrawal induced apoptosis in culture
• abnormal spleen cellularity (MGI Ref ID J:132819)
  • increase in the number of HSV-1 specific T cells in the spleen but not lymph nodes after infection
• increased B cell number (MGI Ref ID J:132819)
  • 2- to 4- fold increase in B220+ positive cells
• hematopoietic system phenotype
• abnormal CD4-positive T cell number (MGI Ref ID J:132819)
  • 2- to 4- fold increase
• abnormal spleen cellularity (MGI Ref ID J:132819)
  • increase in the number of HSV-1 specific T cells in the spleen but not lymph nodes after infection
• increased B cell number (MGI Ref ID J:132819)
  • 2- to 4- fold increase in B220+ positive cells

View Research Applications

Research Applications

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

Bcl2l11^tm1.1Ast related

Apoptosis Research
Endogenous Regulators

Cancer Research
Genes Regulating Growth and Proliferation

Immunology and Inflammation Research
Autoimmunity
Intracellular Signaling Molecules

Internal/Organ Research
Kidney Defects (polycystic kidney disease)
Spleen Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Bcl2l11tm1.1Ast
Allele Name		targeted mutation 1.1, Andreas Strasser
Allele Type		Targeted (knock-out)
Common Name(s)		bim-;
Mutation Made By		Andreas Strasser,   Walter and Eliza Hall Inst of Med Res
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Bcl2l11, BCL2-like 11 (apoptosis facilitator)
Chromosome		2
Gene Common Name(s)		1500006F24Rik; BAM; BIM; BIM-alpha6; BIM-beta6; BIM-beta7; BOD; Bcl2 interacting mediator of cell death; Bim; BimEL; BimL; RIKEN cDNA 1500006F24 gene;
Molecular Note		Insertion of a floxed PGK-neomycin cassette deleted the exon encoding the BH3 domain. Cre-mediated recombination in vivo subsequently removed the inserted cassette. In the final allele a single loxP site remains in place of the exon. Immunoblot analysis using a rat monoclonal antibody did not detect full-length protein, but did detect a small amount of a truncated polypeptide in spleen cells from homozygous mutant mice. [MGI Ref ID J:58641]

Genotyping

Genotyping Information

Genotyping Protocols

Bcl2l11^tm1.1Ast, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Bouillet P; Metcalf D; Huang DC; Tarlinton DM; Kay TW; Kontgen F; Adams JM; Strasser A. 1999. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286(5445):1735-8. [PubMed: 10576740]  [MGI Ref ID J:58641]

Additional References

Akiyama T; Bouillet P; Miyazaki T; Kadono Y; Chikuda H; Chung UI; Fukuda A; Hikita A; Seto H; Okada T; Inaba T; Sanjay A; Baron R; Kawaguchi H; Oda H; Nakamura K; Strasser A; Tanaka S. 2003. Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim. EMBO J 22(24):6653-6664. [PubMed: 14657036]  [MGI Ref ID J:87072]

Bouillet P; Purton JF; Godfrey DI; Zhang LC; Coultas L; Puthalakath H; Pellegrini M; Cory S; Adams JM; Strasser A. 2002. BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415(6874):922-6. [PubMed: 11859372]  [MGI Ref ID J:74991]

Bouillet P; Zhang LC; Huang DC; Webb GC; Bottema CD; Shore P; Eyre HJ; Sutherland GR; Adams JM. 2001. Gene structure alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim. Mamm Genome 12(2):163-8. [PubMed: 11210187]  [MGI Ref ID J:69112]

Bcl2l11^tm1.1Ast related

Akiyama T; Bouillet P; Miyazaki T; Kadono Y; Chikuda H; Chung UI; Fukuda A; Hikita A; Seto H; Okada T; Inaba T; Sanjay A; Baron R; Kawaguchi H; Oda H; Nakamura K; Strasser A; Tanaka S. 2003. Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim. EMBO J 22(24):6653-6664. [PubMed: 14657036]  [MGI Ref ID J:87072]

Alfredsson J; Puthalakath H; Martin H; Strasser A; Nilsson G. 2005. Proapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation. Cell Death Differ 12(2):136-44. [PubMed: 15592435]  [MGI Ref ID J:106372]

Barone MC; Desouza LA; Freeman RS. 2008. Pin1 promotes cell death in NGF-dependent neurons through a mechanism requiring c-Jun activity. J Neurochem 106(2):734-45. [PubMed: 18419764]  [MGI Ref ID J:139389]

Bauer A; Villunger A; Labi V; Fischer SF; Strasser A; Wagner H; Schmid RM; Hacker G. 2006. The NF-kappaB regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells. Proc Natl Acad Sci U S A 103(29):10979-84. [PubMed: 16832056]  [MGI Ref ID J:111822]

Bouillet P; Cory S; Zhang LC; Strasser A; Adams JM. 2001. Degenerative Disorders Caused by Bcl-2 Deficiency Prevented by Loss of Its BH3-Only Antagonist Bim. Dev Cell 1(5):645-53. [PubMed: 11709185]  [MGI Ref ID J:73316]

Bouillet P; Robati M; Bath M; Strasser A. 2005. Polycystic kidney disease prevented by transgenic RNA interference. Cell Death Differ 12(7):831-3. [PubMed: 15818405]  [MGI Ref ID J:128559]

Chang KC; Unsinger J; Davis CG; Schwulst SJ; Muenzer JT; Strasser A; Hotchkiss RS. 2007. Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis. FASEB J 21(3):708-19. [PubMed: 17307841]  [MGI Ref ID J:134855]

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]

Corazza N; Jakob S; Schaer C; Frese S; Keogh A; Stroka D; Kassahn D; Torgler R; Mueller C; Schneider P; Brunner T. 2006. TRAIL receptor-mediated JNK activation and Bim phosphorylation critically regulate Fas-mediated liver damage and lethality. J Clin Invest 116(9):2493-9. [PubMed: 16955144]  [MGI Ref ID J:114519]

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]

Coultas L; Terzano S; Thomas T; Voss A; Reid K; Stanley EG; Scott CL; Bouillet P; Bartlett P; Ham J; Adams JM; Strasser A. 2007. Hrk/DP5 contributes to the apoptosis of select neuronal populations but is dispensable for haematopoietic cell apoptosis. J Cell Sci 120(Pt 12):2044-52. [PubMed: 17535852]  [MGI Ref ID J:124044]

Craxton A; Draves KE; Clark EA. 2007. Bim regulates BCR-induced entry of B cells into the cell cycle. Eur J Immunol 37(10):2715-22. [PubMed: 17705137]  [MGI Ref ID J:125270]

Craxton A; Draves KE; Gruppi A; Clark EA. 2005. BAFF regulates B cell survival by downregulating the BH3-only family member Bim via the ERK pathway. J Exp Med 202(10):1363-74. [PubMed: 16301744]  [MGI Ref ID J:118846]

Doonan F; Donovan M; Gomez-Vicente V; Bouillet P; Cotter TG. 2007. Bim expression indicates the pathway to retinal cell death in development and degeneration. J Neurosci 27(40):10887-94. [PubMed: 17913922]  [MGI Ref ID J:125591]

Egle A; Harris AW; Bouillet P; Cory S. 2004. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci U S A 101(16):6164-9. [PubMed: 15079075]  [MGI Ref ID J:89600]

Enders A; Bouillet P; Puthalakath H; Xu Y; Tarlinton DM; Strasser A. 2003. Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells. J Exp Med 198(7):1119-26. [PubMed: 14517273]  [MGI Ref ID J:86002]

Erlacher M; Labi V; Manzl C; Bock G; Tzankov A; Hacker G; Michalak E; Strasser A; Villunger A. 2006. Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during lymphocyte development, in apoptosis induction. J Exp Med 203(13):2939-51. [PubMed: 17178918]  [MGI Ref ID J:120274]

Erlacher M; Michalak EM; Kelly PN; Labi V; Niederegger H; Coultas L; Adams JM; Strasser A; Villunger A. 2005. BH3-only proteins Puma and Bim are rate-limiting for gamma-radiation- and glucocorticoid-induced apoptosis of lymphoid cells in vivo. Blood 106(13):4131-8. [PubMed: 16118324]  [MGI Ref ID J:124060]

Fischer SF; Belz GT; Strasser A. 2008. BH3-only protein Puma contributes to death of antigen-specific T cells during shutdown of an immune response to acute viral infection. Proc Natl Acad Sci U S A 105(8):3035-40. [PubMed: 18287039]  [MGI Ref ID J:132819]

Gallo EM; Winslow MM; Cante-Barrett K; Radermacher AN; Ho L; McGinnis L; Iritani B; Neilson JR; Crabtree GR. 2007. Calcineurin sets the bandwidth for discrimination of signals during thymocyte development. Nature 450(7170):731-5. [PubMed: 18046413]  [MGI Ref ID J:130376]

Gavalda N; Perez-Navarro E; Garcia-Martinez JM; Marco S; Benito A; Alberch J. 2008. Bax deficiency promotes an up-regulation of Bim(EL) and Bak during striatal and cortical postnatal development, and after excitotoxic injury. Mol Cell Neurosci 37(4):663-72. [PubMed: 18272391]  [MGI Ref ID J:135298]

Hubner A; Barrett T; Flavell RA; Davis RJ. 2008. Multisite phosphorylation regulates Bim stability and apoptotic activity. Mol Cell 30(4):415-25. [PubMed: 18498746]  [MGI Ref ID J:137061]

Hughes P; Robati M; Lu W; Zhou J; Strasser A; Bouillet P. 2006. Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms. Cell Death Differ 13(7):1123-7. [PubMed: 16282979]  [MGI Ref ID J:126158]

Hughes PD; Belz GT; Fortner KA; Budd RC; Strasser A; Bouillet P. 2008. Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity 28(2):197-205. [PubMed: 18275830]  [MGI Ref ID J:132218]

Huntington ND; Puthalakath H; Gunn P; Naik E; Michalak EM; Smyth MJ; Tabarias H; Degli-Esposti MA; Dewson G; Willis SN; Motoyama N; Huang DC; Nutt SL; Tarlinton DM; Strasser A. 2007. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Nat Immunol 8(8):856-863. [PubMed: 17618288]  [MGI Ref ID J:123409]

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]

Hutcheson J; Scatizzi JC; Siddiqui AM; Haines GK rd; Wu T; Li QZ; Davis LS; Mohan C; Perlman H. 2008. Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity. Immunity 28(2):206-17. [PubMed: 18275831]  [MGI Ref ID J:132217]

Jin H; Carrio R; Yu A; Malek TR. 2004. Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. J Immunol 173(1):657-65. [PubMed: 15210829]  [MGI Ref ID J:90963]

Kiss I; Oskolas H; Toth R; Bouillet P; Toth K; Fulop A; Scholtz B; Ledent C; Fesus L; Szondy Z. 2006. Adenosine A2A receptor-mediated cell death of mouse thymocytes involves adenylate cyclase and Bim and is negatively regulated by Nur77. Eur J Immunol 36(6):1559-71. [PubMed: 16673448]  [MGI Ref ID J:115069]

Koralov SB; Muljo SA; Galler GR; Krek A; Chakraborty T; Kanellopoulou C; Jensen K; Cobb BS; Merkenschlager M; Rajewsky N; Rajewsky K. 2008. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 132(5):860-74. [PubMed: 18329371]  [MGI Ref ID J:135783]

Labi V; Erlacher M; Kiessling S; Manzl C; Frenzel A; O'Reilly L; Strasser A; Villunger A. 2008. Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development. J Exp Med 205(3):641-55. [PubMed: 18299399]  [MGI Ref ID J:133084]

Marechal Y; Pesesse X; Jia Y; Pouillon V; Perez-Morga D; Daniel J; Izui S; Cullen PJ; Leo O; Luo HR; Erneux C; Schurmans S. 2007. Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells. Proc Natl Acad Sci U S A 104(35):13978-83. [PubMed: 17709751]  [MGI Ref ID J:124904]

Marsden VS; O'Connor L; O'Reilly LA; Silke J; Metcalf D; Ekert PG; Huang DC; Cecconi F; Kuida K; Tomaselli KJ; Roy S; Nicholson DW; Vaux DL; Bouillet P; Adams JM; Strasser A. 2002. Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature 419(6907):634-7. [PubMed: 12374983]  [MGI Ref ID J:131246]

Naik E; Michalak EM; Villunger A; Adams JM; Strasser A. 2007. Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa. J Cell Biol 176(4):415-24. [PubMed: 17283183]  [MGI Ref ID J:119726]

Ohgushi M; Kuroki S; Fukamachi H; O'Reilly LA; Kuida K; Strasser A; Yonehara S. 2005. Transforming growth factor beta-dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells. Mol Cell Biol 25(22):10017-28. [PubMed: 16260615]  [MGI Ref ID J:102384]

Oliver PM; Vass T; Kappler J; Marrack P. 2006. Loss of the proapoptotic protein, Bim, breaks B cell anergy. J Exp Med 203(3):731-41. [PubMed: 16520387]  [MGI Ref ID J:123717]

Oliver PM; Wang M; Zhu Y; White J; Kappler J; Marrack P. 2004. Loss of Bim allows precursor B cell survival but not precursor B cell differentiation in the absence of interleukin 7. J Exp Med 200(9):1179-87. [PubMed: 15520248]  [MGI Ref ID J:94909]

Pellegrini M; Belz G; Bouillet P; Strasser A. 2003. Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim. Proc Natl Acad Sci U S A 100(24):14175-80. [PubMed: 14623954]  [MGI Ref ID J:86700]

Pellegrini M; Bouillet P; Robati M; Belz GT; Davey GM; Strasser A. 2004. Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. J Exp Med 200(9):1189-95. [PubMed: 15504823]  [MGI Ref ID J:94907]

Perier C; Bove J; Wu DC; Dehay B; Choi DK; Jackson-Lewis V; Rathke-Hartlieb S; Bouillet P; Strasser A; Schulz JB; Przedborski S; Vila M. 2007. Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease. Proc Natl Acad Sci U S A 104(19):8161-6. [PubMed: 17483459]  [MGI Ref ID J:121592]

Reckling S; Divanovic S; Karp CL; Wojciechowski S; Belkaid Y; Hildeman D. 2008. Proapoptotic Bcl-2 family member Bim promotes persistent infection and limits protective immunity. Infect Immun 76(3):1179-85. [PubMed: 18086806]  [MGI Ref ID J:131639]

Redmond WL; Wei CH; Kreuwel HT; Sherman LA. 2008. The apoptotic pathway contributing to the deletion of naive CD8 T cells during the induction of peripheral tolerance to a cross-presented self-antigen. J Immunol 180(8):5275-82. [PubMed: 18390708]  [MGI Ref ID J:134242]

Sandoval H; Thiagarajan P; Dasgupta SK; Schumacher A; Prchal JT; Chen M; Wang J. 2008. Essential role for Nix in autophagic maturation of erythroid cells. Nature 454(7201):232-5. [PubMed: 18454133]  [MGI Ref ID J:137609]

Steckley D; Karajgikar M; Dale LB; Fuerth B; Swan P; Drummond-Main C; Poulter MO; Ferguson SS; Strasser A; Cregan SP. 2007. Puma is a dominant regulator of oxidative stress induced Bax activation and neuronal apoptosis. J Neurosci 27(47):12989-99. [PubMed: 18032672]  [MGI Ref ID J:127640]

Uldrich AP; Berzins SP; Malin MA; Bouillet P; Strasser A; Smyth MJ; Boyd RL; Godfrey DI. 2006. Antigen challenge inhibits thymic emigration. J Immunol 176(8):4553-61. [PubMed: 16585545]  [MGI Ref ID J:131166]

Uldrich AP; Crowe NY; Kyparissoudis K; Pellicci DG; Zhan Y; Lew AM; Bouillet P; Strasser A; Smyth MJ; Godfrey DI. 2005. NKT cell stimulation with glycolipid antigen in vivo: costimulation-dependent expansion, Bim-dependent contraction, and hyporesponsiveness to further antigenic challenge. J Immunol 175(5):3092-101. [PubMed: 16116198]  [MGI Ref ID J:113331]

Van Dyken SJ; Green RS; Marth JD. 2007. Structural and mechanistic features of protein O glycosylation linked to CD8+ T-cell apoptosis. Mol Cell Biol 27(3):1096-111. [PubMed: 17101770]  [MGI Ref ID J:118162]

Villunger A; Marsden VS; Zhan Y; Erlacher M; Lew AM; Bouillet P; Berzins S; Godfrey DI; Heath WR; Strasser A. 2004. Negative selection of semimature CD4(+)8(-)HSA+ thymocytes requires the BH3-only protein Bim but is independent of death receptor signaling. Proc Natl Acad Sci U S A 101(18):7052-7. [PubMed: 15118096]  [MGI Ref ID J:89947]

Weant AE; Michalek RD; Khan IU; Holbrook BC; Willingham MC; Grayson JM. 2008. Apoptosis regulators Bim and Fas function concurrently to control autoimmunity and CD8+ T cell contraction. Immunity 28(2):218-30. [PubMed: 18275832]  [MGI Ref ID J:132216]

Wojciechowski S; Jordan MB; Zhu Y; White J; Zajac AJ; Hildeman DA. 2006. Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory. Eur J Immunol 36(7):1694-706. [PubMed: 16761315]  [MGI Ref ID J:115833]

Wojciechowski S; Tripathi P; Bourdeau T; Acero L; Grimes HL; Katz JD; Finkelman FD; Hildeman DA. 2007. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J Exp Med 204(7):1665-75. [PubMed: 17591857]  [MGI Ref ID J:125868]

Xiang Z; Cutler AJ; Brownlie RJ; Fairfax K; Lawlor KE; Severinson E; Walker EU; Manz RA; Tarlinton DM; Smith KG. 2007. FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis. Nat Immunol 8(4):419-29. [PubMed: 17322888]  [MGI Ref ID J:120734]

Xiao C; Srinivasan L; Calado DP; Patterson HC; Zhang B; Wang J; Henderson JM; Kutok JL; Rajewsky K. 2008. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9(4):405-14. [PubMed: 18327259]  [MGI Ref ID J:133215]

Yano T; Ito K; Fukamachi H; Chi XZ; Wee HJ; Inoue K; Ida H; Bouillet P; Strasser A; Bae SC; Ito Y. 2006. The RUNX3 tumor suppressor upregulates Bim in gastric epithelial cells undergoing transforming growth factor beta-induced apoptosis. Mol Cell Biol 26(12):4474-88. [PubMed: 16738314]  [MGI Ref ID J:109611]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	The resulting chimeric animals were crossed to a C57BL/6 Cre-deleter strain to remove the neo cassette, and then backcrossed to C57BL/6 for 13 generations. Donating Investigator reports that homozygous females, although fertile, tend to be poor mothers; uses the following breeding scheme: heterozygous females X homozygous males . 5-7 pups per litter.
Mating System	Heterozygote 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

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

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

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

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.

No Liability

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

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.