JAX
Mouse Strain Datasheet - 004525
B6.129S1-Bcl2l11tm1.1Ast/J
Also Known As: Bim KO
These Bcl2l11tm1.1Ast knock-out mice exhibit progressive systemic autoimmune disease. They may be useful in studies of apoptosis, degenerative and autoimmune diseases, including lupus erythematosus and autoimmune kidney disease.
Donating Investigator
Andreas Strasser, Walter and Eliza Hall Inst of Med Res
Genetic overview
| Genetic Background | Generation |
|---|---|
|
N15+F2
|
Bcl2l11tm1.1Ast
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Bcl2l11 | BCL2-like 11 (apoptosis facilitator) |
Research Applications
- Apoptosis Research
- Cancer Research
- Immunology, Inflammation and Autoimmunity Research
- Internal/Organ Research
Base Price
Starting at:
| $263.00 Domestic price for female |
| $526.00 Domestic price for breeder pair |
Detailed 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 Suggestions
Selected References
- 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: 10576740MGI: J:58641
Bcl2l11tm1.1Ast
Allele Symbol: Bcl2l11tm1.1Ast
| Allele Name | targeted mutation 1.1, Andreas Strasser |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | bim- |
| Gene Symbol and Name | Bcl2l11, BCL2-like 11 (apoptosis facilitator) |
| Gene Synonym(s) | 1500006F24Rik; 1500006F24Rik; BAM; BIM; BOD; Bcl2 interacting mediator of cell death; Bim; Bim; BimL; Bod; RIKEN cDNA 1500006F24 gene |
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> |
| Chromosome | 2 |
| 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. |
| Mutations Made By | Andreas Strasser, Walter and Eliza Hall Inst of Med Res |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
Genotype: Bcl2l11tm1.1Ast related
- Apoptosis Research
- Endogenous Regulators
- Cancer Research
- Genes Regulating Growth and Proliferation
- Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
- Intracellular Signaling Molecules
- Internal/Organ Research
- Kidney Defects
- polycystic kidney disease
- Spleen Defects
- Kidney Defects
Mammalian Phenotype Terms by Genotype
Genotype: Bcl2l11tm1.1Ast/Bcl2l11+
B6.129S1-Bcl2l11tm1.1Ast
hematopoietic system phenotype
- increased leukocyte cell number
- increased white blood cells numbers (<1.5 fold) (MGI Ref ID J:153846)
- increased spleen weight
- increase in spleen weight (<2 fold) (MGI Ref ID J:153846)
immune system phenotype
- immune system phenotype
- normal in vitro survival assays with several cytotoxic stimuli on sorted thymocyte and B cell populations (MGI Ref ID J:153846)
- increased leukocyte cell number
- increased white blood cells numbers (<1.5 fold) (MGI Ref ID J:153846)
- increased spleen weight
- increase in spleen weight (<2 fold) (MGI Ref ID J:153846)
Genotype: Bcl2l11tm1.1Ast/Bcl2l11tm1.1Ast
B6.129S1-Bcl2l11tm1.1Ast
immune system phenotype
- abnormal B cell morphology
- (MGI Ref ID J:133084)
- abnormal NK cell morphology
- following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells (MGI Ref ID J:123409)
- abnormal leukopoiesis
- irradiated mice reconstituted with mutant fetal liver cells have a 2- to 4- fold increase in lymphocyte and myeloid cell numbers compared to controls (MGI Ref ID J:73316)
- abnormal lymphocyte physiology
- survival of mature resting T and B cells in the absence of cytokines is improved compared to wild-type cells (MGI Ref ID J:73316)
- abnormal response to infection
- following infection with mouse cytomegalovirus infection, more NK cell survive at day 10 and 14 than in wild-type mice (MGI Ref ID J:123409)
- decreased B cell apoptosis
- about 10-fold more B cells cultured without cytokines are alive after six days compared to controls (MGI Ref ID J:73316)
- decreased T cell apoptosis
- immune system phenotype
- normal in vitro survival assays with several cytotoxic stimuli on sorted thymocyte and B cell populations (MGI Ref ID J:153846)
- increased NK cell number
- mice have a higher percent of KLRG1+CD27- NK cells in the spleen, liver and bone marrow compared to wild-type mice (MGI Ref ID J:123409)
- increased immature B cell number
- (MGI Ref ID J:133084)
- increased leukocyte cell number
- increased white blood cells numbers (>3 fold) (MGI Ref ID J:153846)
- increased mature B cell number
- (MGI Ref ID J:133084)
- increased regulatory T cell number
- at 6 months (MGI Ref ID J:208318)
- increased spleen weight
- increased spleen weight (>2.5 fold) (MGI Ref ID J:153846)
- increased transitional stage B cell number
homeostasis/metabolism phenotype
- decreased physiological sensitivity to xenobiotic
- NK cells are more resistant to LY294002-induced apoptosis (MGI Ref ID J:123409)
cellular phenotype
- decreased B cell apoptosis
- about 10-fold more B cells cultured without cytokines are alive after six days compared to controls (MGI Ref ID J:73316)
- decreased T cell apoptosis
- decreased apoptosis
nervous system phenotype
- abnormal sympathetic neuron morphology
- sympathetic neurons are partially protected from apoptosis induced by the withdrawal of nerve growth factor (MGI Ref ID J:124044)
hematopoietic system phenotype
- abnormal B cell morphology
- (MGI Ref ID J:133084)
- abnormal NK cell morphology
- following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells (MGI Ref ID J:123409)
- abnormal leukopoiesis
- irradiated mice reconstituted with mutant fetal liver cells have a 2- to 4- fold increase in lymphocyte and myeloid cell numbers compared to controls (MGI Ref ID J:73316)
- abnormal lymphocyte physiology
- survival of mature resting T and B cells in the absence of cytokines is improved compared to wild-type cells (MGI Ref ID J:73316)
- decreased B cell apoptosis
- about 10-fold more B cells cultured without cytokines are alive after six days compared to controls (MGI Ref ID J:73316)
- decreased T cell apoptosis
- increased NK cell number
- mice have a higher percent of KLRG1+CD27- NK cells in the spleen, liver and bone marrow compared to wild-type mice (MGI Ref ID J:123409)
- increased immature B cell number
- (MGI Ref ID J:133084)
- increased leukocyte cell number
- increased white blood cells numbers (>3 fold) (MGI Ref ID J:153846)
- increased mature B cell number
- (MGI Ref ID J:133084)
- increased regulatory T cell number
- at 6 months (MGI Ref ID J:208318)
- increased spleen weight
- increased spleen weight (>2.5 fold) (MGI Ref ID J:153846)
Genotype: Bcl2l11tm1.1Ast/Bcl2l11tm1.1Ast
B6.129S1-Bcl2l11tm1.1Ast/J
immune system phenotype
- decreased T cell apoptosis
- increased viability of CD4 and CD8 T cells during in vitro culture of T cells purified from spleen and lymph nodes (MGI Ref ID J:153652)
- increased B cell number
- a large increase in the number of B cells in the spleen (MGI Ref ID J:153652)
- increased CD4-positive, alpha beta T cell number
- a large increase in the number of CD4-positive T cells in the spleen (MGI Ref ID J:153652)
- increased CD8-positive, alpha-beta T cell number
- a large increase in the number of CD8-positive T cells in the spleen (MGI Ref ID J:153652)
- increased splenocyte number
- increased number of splenocytes (>3 fold) (MGI Ref ID J:153652)
hematopoietic system phenotype
- decreased T cell apoptosis
- increased viability of CD4 and CD8 T cells during in vitro culture of T cells purified from spleen and lymph nodes (MGI Ref ID J:153652)
- increased B cell number
- a large increase in the number of B cells in the spleen (MGI Ref ID J:153652)
- increased CD4-positive, alpha beta T cell number
- a large increase in the number of CD4-positive T cells in the spleen (MGI Ref ID J:153652)
- increased CD8-positive, alpha-beta T cell number
- a large increase in the number of CD8-positive T cells in the spleen (MGI Ref ID J:153652)
- increased splenocyte number
- increased number of splenocytes (>3 fold) (MGI Ref ID J:153652)
cellular phenotype
- decreased T cell apoptosis
- increased viability of CD4 and CD8 T cells during in vitro culture of T cells purified from spleen and lymph nodes (MGI Ref ID J:153652)
Genotype: Bcl2l11tm1.1Ast/Bcl2l11tm1.1Ast
B6.129-Bcl2l11tm1.1Ast/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 is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Bcl2l11tm1.1Ast/Bcl2l11+
involves: 129S1/Sv * C57BL/6
mortality/aging
- premature death
- by 1 year of age 35% of heterozygotes are terminally ill (MGI Ref ID J:58641)
immune system phenotype
- abnormal lymphocyte physiology
- pre-T cells cultured without cytokines or with ionomycin or taxol survive better than wild-type cells but not as well as homozygous cells (MGI Ref ID J:58641)
- glomerulonephritis
- by 1 year of about 85% of terminally ill heterozygotes have immune complex glomerulonephritis (MGI Ref ID J:58641)
- increased IgA level
- increased at 6 to 12 months of age but less than in homozygous mice (MGI Ref ID J:58641)
- increased IgG level
- increased at 6 to 12 months of age but less than in homozygous mice (MGI Ref ID J:58641)
- increased IgM level
- increased at 6 to 12 months of age but less than in homozygous mice (MGI Ref ID J:58641)
- increased susceptibility to autoimmune disorder
- older heterozygotes develop lymphadenopathy (MGI Ref ID J:58641)
- vasculitis
- about 20% of terminally ill heterozygotes show signs of vasculitis or cardiac infarction (MGI Ref ID J:58641)
renal/urinary system phenotype
- glomerulonephritis
- by 1 year of about 85% of terminally ill heterozygotes have immune complex glomerulonephritis (MGI Ref ID J:58641)
cardiovascular system phenotype
- vasculitis
- about 20% of terminally ill heterozygotes show signs of vasculitis or cardiac infarction (MGI Ref ID J:58641)
hematopoietic system phenotype
- abnormal lymphocyte physiology
- pre-T cells cultured without cytokines or with ionomycin or taxol survive better than wild-type cells but not as well as homozygous cells (MGI Ref ID J:58641)
- increased IgA level
- increased at 6 to 12 months of age but less than in homozygous mice (MGI Ref ID J:58641)
- increased IgG level
- increased at 6 to 12 months of age but less than in homozygous mice (MGI Ref ID J:58641)
- increased IgM level
- increased at 6 to 12 months of age but less than in homozygous mice (MGI Ref ID J:58641)
Genotype: Bcl2l11tm1.1Ast/Bcl2l11tm1.1Ast
involves: 129S1/Sv
endocrine/exocrine gland phenotype
- abnormal involution of the mammary gland
- delay in postlactational remodeling of the mammary gland (MGI Ref ID J:235354)
immune system phenotype
- abnormal CD4-positive, alpha beta T cell number
- 2- to 4- fold increase (MGI Ref ID J:132819)
- abnormal CD8-positive, alpha-beta T cell physiology
- HSV-1 antigen specific CD8+ T cells show nearly complete resistance to cytokine withdrawal induced apoptosis in culture (MGI Ref ID J:132819)
- abnormal splenic cell ratio
- increase in the number of HSV-1 specific T cells in the spleen but not lymph nodes after infection (MGI Ref ID J:132819)
- increased B cell number
- 2- to 4- fold increase in B220+ positive cells (MGI Ref ID J:132819)
hematopoietic system phenotype
- abnormal CD4-positive, alpha beta T cell number
- 2- to 4- fold increase (MGI Ref ID J:132819)
- abnormal CD8-positive, alpha-beta T cell physiology
- HSV-1 antigen specific CD8+ T cells show nearly complete resistance to cytokine withdrawal induced apoptosis in culture (MGI Ref ID J:132819)
- abnormal splenic cell ratio
- increase in the number of HSV-1 specific T cells in the spleen but not lymph nodes after infection (MGI Ref ID J:132819)
- hematopoietic system phenotype
- unlike in Bnip3ltm1Ney homozygotes, reticulocytes clearance of mitochondria is normal (MGI Ref ID J:141545)
- increased B cell number
- 2- to 4- fold increase in B220+ positive cells (MGI Ref ID J:132819)
integument phenotype
- abnormal involution of the mammary gland
- delay in postlactational remodeling of the mammary gland (MGI Ref ID J:235354)
Genotype: Bcl2l11tm1.1Ast/Bcl2l11tm1.1Ast
involves: 129S1/Sv * C57BL/6
mortality/aging
- embryonic lethality during organogenesis, incomplete penetrance
- Background Sensitivity - about half die before E10; however, this percentage is highly variable and background dependent (MGI Ref ID J:58641)
- premature death
- by 1 year of age 55% of homozygotes are terminally ill with 85% of these developing kidney disease (immune complex glomerulonephritis) (MGI Ref ID J:58641)
immune system phenotype
- abnormal B cell proliferation
- anti-CD40 B cell proliferation is increased 3- to 5- fold in the presence of IL-21, which does not occur in wild-type controls (MGI Ref ID J:90963)
- abnormal lymphocyte physiology
- 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 (MGI Ref ID J:58641)
- 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 (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 (MGI Ref ID J:58641)
- abnormal plasma cell morphology
- 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 (MGI Ref ID J:58641)
- abnormal spleen morphology
- (MGI Ref ID J:58641)
- abnormal splenic cell ratio
- T1:follicular B cell ratio is higher than wild-type (MGI Ref ID J:132217)
- decreased B cell apoptosis
- IL-21 fails to induce apoptosis in LPS-activated B cells as it does in wild-type mice (MGI Ref ID J:90963)
- decreased double-positive T cell number
- 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 (MGI Ref ID J:58641)
- enlarged spleen
- in older homozygotes spleen size is increased 5- to 10-fold (MGI Ref ID J:58641)
- glomerulonephritis
- by 1 year of about 85% of terminally ill homozygotes have immune complex glomerulonephritis (MGI Ref ID J:58641)
- increased B cell number
- 2- to 4-fold increase (MGI Ref ID J:58641)
- increased CD4-positive, alpha beta T cell number
- 2- to 3-fold increase in the number of CD4+ T cells is seen in adult mice (MGI Ref ID J:58641)
- increased CD8-positive, alpha-beta T cell number
- 2- to 3-fold increase in the number of CD8+ T cells is seen in adult mice (MGI Ref ID J:58641)
- increased IgA level
- elevated about 3-fold at 6 to 12 months of age (MGI Ref ID J:58641)
- increased IgG level
- elevated about 10-fold at 6 to 12 months of age (MGI Ref ID J:58641)
- increased IgM level
- elevated about 3-fold at 6 to 12 months of age (MGI Ref ID J:58641)
- increased T cell number
- 2- to 4-fold increase involving mostly mature T cells is seen in adult mice (MGI Ref ID J:58641)
- increased anti-double stranded DNA antibody level
- anti-SsDNA IgM and IgG antibodies are increased compared to wild-type (MGI Ref ID J:132217)
- increased anti-histone antibody level
- increased compared to wild-type (MGI Ref ID J:132217)
- increased anti-nuclear antigen antibody level
- anti-nuclear antibodies are increased compared to wild-type (MGI Ref ID J:132217)
- increased anti-single stranded DNA antibody level
- anti-ssDNA IgM and IgG antibodies are increased compared to wild-type (MGI Ref ID J:132217)
- increased autoantibody level
- total anti-IgM antibody levels are increased compared to wild-type (MGI Ref ID J:132217)
- increased double-negative T cell number
- 2- to 3-fold increase is seen in adult mice (MGI Ref ID J:58641)
- increased follicular B cell number
- higher in spleen relative to wild-type and Faslpr homozygotes (MGI Ref ID J:132217)
- increased granulocyte number
- 2- to 4-fold increase (MGI Ref ID J:58641)
- increased immature B cell number
- plasmablast numbers in spleen are increased relative to wild-type (MGI Ref ID J:132217)
- increased inflammatory response
- (MGI Ref ID J:58641)
- increased leukocyte cell number
- blood, spleen, and lymph node leukocyte numbers are elevated several fold mostly as a result of increased B and T cell counts (MGI Ref ID J:58641)
- however, the number of red cells is normal and the number of hematopoietic progenitor cells in the bone marrow is similar to wild-type (MGI Ref ID J:58641)
- these cells are mostly small, noncycling cells suggesting an increase in cell survival rather than proliferation (MGI Ref ID J:58641)
- increased marginal zone B cell number
- higher in spleen relative to wild-type and Faslpr homozygotes (MGI Ref ID J:132217)
- increased monocyte cell number
- 2- to 4-fold increase (MGI Ref ID J:58641)
- increased splenocyte number
- increased susceptibility to autoimmune disorder
- older homozygotes develop lymphadenopathy (MGI Ref ID J:58641)
- increased transitional stage B cell number
- higher numbers of T1 and T2 B cells in spleen relative to wild-type (MGI Ref ID J:132217)
- spleen hyperplasia
- seen in older homozygotes with plasma cells most severely affected (MGI Ref ID J:58641)
- vasculitis
- about 20% of terminally ill homozygotes show signs of vasculitis or cardiac infarction (MGI Ref ID J:58641)
renal/urinary system phenotype
- abnormal kidney morphology
- abnormal renal glomerulus basement membrane morphology
- IgG deposits mainly localized to glomerular basement membrane are increased relative to wild-type (MGI Ref ID J:132217)
- abnormal renal glomerulus morphology
- hypercellularity is seen in homozygotes with kidney disease (MGI Ref ID J:58641)
- dilated renal tubules
- eosinophilic deposits are seen in dilated renal tubules in homozygotes with kidney disease (MGI Ref ID J:58641)
- expanded mesangial matrix
- (MGI Ref ID J:58641)
- glomerular crescent
- proliferation of capsular epithelial cells is seen in homozygotes with kidney disease (MGI Ref ID J:58641)
- glomerulonephritis
- by 1 year of about 85% of terminally ill homozygotes have immune complex glomerulonephritis (MGI Ref ID J:58641)
- increased renal glomerulus apoptosis
- higher numbers of apoptotic cells are detected in glomeruli compared to wild-type (MGI Ref ID J:132217)
- renal cast
- dilated renal tubules contain eosinophilic casts (MGI Ref ID J:58641)
homeostasis/metabolism phenotype
- increased blood urea nitrogen level
- (MGI Ref ID J:58641)
nervous system phenotype
- nervous system phenotype
- unlike mice homozygous for Bbc3tm1Ast neuron sensitivity to oxidative stressor induced apoptosis is similar to controls (MGI Ref ID J:127640)
hematopoietic system phenotype
- abnormal B cell proliferation
- anti-CD40 B cell proliferation is increased 3- to 5- fold in the presence of IL-21, which does not occur in wild-type controls (MGI Ref ID J:90963)
- abnormal lymphocyte physiology
- 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 (MGI Ref ID J:58641)
- 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 (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 (MGI Ref ID J:58641)
- abnormal plasma cell morphology
- 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 (MGI Ref ID J:58641)
- abnormal spleen morphology
- (MGI Ref ID J:58641)
- abnormal splenic cell ratio
- T1:follicular B cell ratio is higher than wild-type (MGI Ref ID J:132217)
- decreased B cell apoptosis
- IL-21 fails to induce apoptosis in LPS-activated B cells as it does in wild-type mice (MGI Ref ID J:90963)
- decreased double-positive T cell number
- 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 (MGI Ref ID J:58641)
- enlarged spleen
- in older homozygotes spleen size is increased 5- to 10-fold (MGI Ref ID J:58641)
- increased B cell number
- 2- to 4-fold increase (MGI Ref ID J:58641)
- increased CD4-positive, alpha beta T cell number
- 2- to 3-fold increase in the number of CD4+ T cells is seen in adult mice (MGI Ref ID J:58641)
- increased CD8-positive, alpha-beta T cell number
- 2- to 3-fold increase in the number of CD8+ T cells is seen in adult mice (MGI Ref ID J:58641)
- increased IgA level
- elevated about 3-fold at 6 to 12 months of age (MGI Ref ID J:58641)
- increased IgG level
- elevated about 10-fold at 6 to 12 months of age (MGI Ref ID J:58641)
- increased IgM level
- elevated about 3-fold at 6 to 12 months of age (MGI Ref ID J:58641)
- increased T cell number
- 2- to 4-fold increase involving mostly mature T cells is seen in adult mice (MGI Ref ID J:58641)
- increased double-negative T cell number
- 2- to 3-fold increase is seen in adult mice (MGI Ref ID J:58641)
- increased follicular B cell number
- higher in spleen relative to wild-type and Faslpr homozygotes (MGI Ref ID J:132217)
- increased granulocyte number
- 2- to 4-fold increase (MGI Ref ID J:58641)
- increased immature B cell number
- plasmablast numbers in spleen are increased relative to wild-type (MGI Ref ID J:132217)
- increased leukocyte cell number
- blood, spleen, and lymph node leukocyte numbers are elevated several fold mostly as a result of increased B and T cell counts (MGI Ref ID J:58641)
- however, the number of red cells is normal and the number of hematopoietic progenitor cells in the bone marrow is similar to wild-type (MGI Ref ID J:58641)
- these cells are mostly small, noncycling cells suggesting an increase in cell survival rather than proliferation (MGI Ref ID J:58641)
- increased marginal zone B cell number
- higher in spleen relative to wild-type and Faslpr homozygotes (MGI Ref ID J:132217)
- increased monocyte cell number
- 2- to 4-fold increase (MGI Ref ID J:58641)
- increased splenocyte number
- increased transitional stage B cell number
- higher numbers of T1 and T2 B cells in spleen relative to wild-type (MGI Ref ID J:132217)
- spleen hyperplasia
- seen in older homozygotes with plasma cells most severely affected (MGI Ref ID J:58641)
- thrombocytopenia
- platelet count is reduced to about 1/2 of wild-type; however, megakaryocyte numbers are normal (MGI Ref ID J:58641)
cardiovascular system phenotype
- vasculitis
- about 20% of terminally ill homozygotes show signs of vasculitis or cardiac infarction (MGI Ref ID J:58641)
cellular phenotype
- decreased B cell apoptosis
- IL-21 fails to induce apoptosis in LPS-activated B cells as it does in wild-type mice (MGI Ref ID J:90963)
- increased renal glomerulus apoptosis
- higher numbers of apoptotic cells are detected in glomeruli compared to wild-type (MGI Ref ID J:132217)
References
- 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: 10576740MGI: 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: 14657036MGI: 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: 11859372MGI: 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: 11210187MGI: J:69112
Additional - Bcl2l11tm1.1Ast 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: 14657036MGI: 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: 15592435MGI: J:106372
- Andina N; Conus S; Schneider EM; Fey MF; Simon HU. 2009. Induction of Bim limits cytokine-mediated prolonged survival of neutrophils. Cell Death Differ 16(9):1248-55. PubMed: 19407828MGI: J:164177
- Barnes MJ; Aksoylar H; Krebs P; Bourdeau T; Arnold CN; Xia Y; Khovananth K; Engel I; Sovath S; Lampe K; Laws E; Saunders A; Butcher GW; Kronenberg M; Steinbrecher K; Hildeman D; Grimes HL; Beutler B; Hoebe K. 2010. Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice. J Immunol 184(7):3743-54. PubMed: 20190135MGI: J:160090
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