Description

Strain Information

Former Names C57BL/6-Tg(BCL2)36Wehi/J    (Changed: 24-JAN-06 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Alan Harris,   The Walter & Eliza Hall Inst of Med Res

Appearance
black
Related Genotype: a/a

Description
Expression of the human BCL2 transgene in both T cell and B cell lineages. This transgenic line combines the characteristics of both Tg(BCL2)22Wehi and the Tg(BCL2)25Wehi lines. Hemizygotes show increased numbers of B lymphocytes, Ig-secreting cells and serum Ig, as well as a heightened and prolonged antibody response to immunization. T-cells withstand prolonged culture in the absence of growth factors and are resistant to killing by gamma-radiation, glucocorticoids, ionomycin, PMA and sodium azide but NOT complement, cytotoxic T cells, or Fas ligand. Hemizygotes have a normal total T-cell count and thymic involution rate but show an enhanced response to immunization. These mice serve as a robust source for the production of B-cells, antibodies T-cell lines or hybridomas. Although mice bearing this allele exhibit a mild increase in spontaneous lymphoma and plasmacytoma occurrence (<10% to 18 months) on a (C57BL/6 x SJL)F2 background, on the BALB/c and C57BL/6 backgrounds tumor incidence is insignificant. Hemizygotes on a mixed B6,SJL background (but not on the C57BL/6 background) develop an autoimmune disease characterized by immune complex glomerulonephritis, anti-nuclear antibodies, lymphadenopathy, and myocardial infarction.

Development
The TgN(BCL2)36Wehi transgenic strain was made in the laboratory of Dr. Alan Harris of the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. The transgene construct consisted of the human BCL2 cDNA in association with the Emu immunoglobulin heavy chain enhancer and SV40 promoter. Original background was mix of C57BL/6JWehi and SJL/JWehi. Transgenic mice have been bred to C57BL/6J more than 20 generations.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of BCL2

002319	B6.Cg-Tg(BCL2)22Wehi/J
002320	B6.Cg-Tg(BCL2)25Wehi/J
002318	C.Cg-Tg(BCL2)22Wehi/J
002427	C3H/He-Tg(LCKprBCL2)36Sjk/J
002971	FVB-Tg(BCL2OVARY)1Ah/J

View Strains carrying other alleles of BCL2     (5 strains)

Strains carrying other alleles of SV40

002319	B6.Cg-Tg(BCL2)22Wehi/J
002320	B6.Cg-Tg(BCL2)25Wehi/J
002318	C.Cg-Tg(BCL2)22Wehi/J
003477	C57BL/6J-Tg(SV)419Bri/J
003476	C57BL/6J-Tg(SV)427Bri/J
003268	FVB-Tg(IRS1)1Mhep/J

View Strains carrying other alleles of SV40     (6 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Tg(BCL2)36Wehi/0

        involves: C57BL/6JWehi * SJL/JWehi

• hematopoietic system phenotype
• increased B cell number (MGI Ref ID J:93111)
  • mutants show an excess of B lymphocytes
• increased T cell number (MGI Ref ID J:93111)
  • mutants have an excess of T lymphocytes
• immune system phenotype
• abnormal B cell physiology (MGI Ref ID J:93111)
  • transgenic spleen B cells show prolonged in vitro survival in culture compared to wild-type splenocytes
• increased immunoglobulin level (MGI Ref ID J:93111)
  • mice display increased serum immunoglobulin concentrations
• abnormal T cell physiology (MGI Ref ID J:93111)
  • transgenic T cells show prolonged in vitro survival in culture compared to wild-type T lymphocytes
• increased B cell number (MGI Ref ID J:93111)
  • mutants show an excess of B lymphocytes
• increased T cell number (MGI Ref ID J:93111)
  • mutants have an excess of T lymphocytes
• increased susceptibility to autoimmune disorder (MGI Ref ID J:93111)
  • some transgenic mice develop a systemic autoimmune-like disease
• tumorigenesis
• T cell derived lymphoma (MGI Ref ID J:93111)
  • a few mice develop fatal clonal T cell tumors

View Research Applications

Research Applications

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

Apoptosis Research
Endogenous Regulators

Immunology and Inflammation Research
Intracellular Signaling Molecules

Research Tools
Cancer Research (production of B and T cells, antibodies, and hybridomas)
Immunology and Inflammation Research (production of B cells, antibodies T cell lines, and hybridomas)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(BCL2)36Wehi
Allele Name		transgene insertion 36, Walter and Eliza Hall Institute of Medical Research
Allele Type		Transgenic (random, expressed)
Common Name(s)		E mu-bcl-2-36; Emu-Bcl-2-36;
Mutation Made By		Alan Harris,   The Walter & Eliza Hall Inst of Med Res
Strain of Origin		(C57BL/6JWehi x SJL/JWehi)F2
Expressed Gene		BCL2, B-cell CLL/lymphoma 2, human
Promoter		SV40, E mu enhancer, SV40
General Note		The transgene is expressed in both T cell and B cell lineages. On a C57BL/6 background hemizygotes show increased numbers of B lymphocytes, Ig-secreting cells and serum Ig, as well as a heightened and prolonged antibody response to immunization. T-cells withstand prolonged culture in the absence of growth factors and are resistant to killing by gamma-radiation, glucocorticoids, ionomycin, PMA, and sodium azide, but not complement, cytotoxic T cells, or Fas ligand. These hemizygotes have a normal total T-cell count and thymic involution rate but show an enhanced response to immunization, and serve as a robust source for the production of B-cells, antibodies T-cell lines or hybridomas. Although transgenic mice on a (C57BL/6 x SJL)F2 background exhibit a mild increase in spontaneous lymphoma and plasmacytoma occurrence (<10% to 18 months), on the BALB/c and C57BL/6 backgrounds tumor incidence is insignificant. Hemizygotes on a background involving C57BL/6 and SJL (but not on the C57BL/6 background) develop an autoimmune disease characterized by immune complex glomerulonephritis, anti-nuclear antibodies, lymphadenopathy, and myocardial infarction.
Molecular Note		The transgene construct consists of the human BCL2 cDNA in association with the Emu immunoglobulin heavy chain enhancer and SV40 promoter. [MGI Ref ID J:93111]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(BCL2), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Strasser A; Harris AW; Corcoran LM; Cory S. 1994. Bcl-2 expression promotes B- but not T-lymphoid development in scid mice. Nature 368(6470):457-60. [PubMed: 8133891]  [MGI Ref ID J:17426]

Strasser A; Harris AW; Cory S. 1991. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67(5):889-99. [PubMed: 1959134]  [MGI Ref ID J:69572]

Additional References

Khaled AR; Li WQ; Huang J; Fry TJ; Khaled AS; Mackall CL; Muegge K; Young HA; Durum SK. 2002. Bax deficiency partially corrects interleukin-7 receptor alpha deficiency. Immunity 17(5):561-73. [PubMed: 12433363]  [MGI Ref ID J:93139]

O'Reilly LA; Harris AW; Tarlinton DM; Corcoran LM; Strasser A. 1997. Expression of a bcl-2 transgene reduces proliferation and slows turnover of developing B lymphocytes in vivo. J Immunol 159(5):2301-11. [PubMed: 9278319]  [MGI Ref ID J:93123]

Tan JT; Dudl E; LeRoy E; Murray R; Sprent J; Weinberg KI; Surh CD. 2001. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 98(15):8732-7. [PubMed: 11447288]  [MGI Ref ID J:93058]

Tg(BCL2)36Wehi related

Bell SE; Vigorito E; McAdam S; Reynolds HM; Caraux A; Colucci F; Turner M. 2004. PLCgamma2 regulates Bcl-2 levels and is required for survival rather than differentiation of marginal zone and follicular B cells. Eur J Immunol 34(8):2237-47. [PubMed: 15259021]  [MGI Ref ID J:91772]

Carrio R; Rolle CE; Malek TR. 2007. Non-redundant role for IL-7R signaling for the survival of CD8(+) memory T cells. Eur J Immunol 37(11):3078-88. [PubMed: 17935075]  [MGI Ref ID J:126334]

Cobaleda C; Jochum W; Busslinger M. 2007. Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 449(7161):473-7. [PubMed: 17851532]  [MGI Ref ID J:126362]

Cory S; Harris AW; Strasser A. 1994. Insights from transgenic mice regarding the role of bcl-2 in normal and neoplastic lymphoid cells. Philos Trans R Soc Lond B Biol Sci 345(1313):289-95. [PubMed: 7846127]  [MGI Ref ID J:21062]

Fry TJ; Christensen BL; Komschlies KL; Gress RE; Mackall CL. 2001. Interleukin-7 restores immunity in athymic T-cell-depleted hosts. Blood 97(6):1525-33. [PubMed: 11238086]  [MGI Ref ID J:93170]

Grumont RJ; Rourke IJ; O'Reilly LA; Strasser A; Miyake K; Sha W; Gerondakis S. 1998. B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-kappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogen-activated cells. J Exp Med 187(5):663-74. [PubMed: 9480976]  [MGI Ref ID J:46076]

Janas ML; Hodson D; Stamataki Z; Hill S; Welch K; Gambardella L; Trotman LC; Pandolfi PP; Vigorito E; Turner M. 2008. The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells. J Immunol 180(2):739-46. [PubMed: 18178811]  [MGI Ref ID J:130950]

Khaled AR; Li WQ; Huang J; Fry TJ; Khaled AS; Mackall CL; Muegge K; Young HA; Durum SK. 2002. Bax deficiency partially corrects interleukin-7 receptor alpha deficiency. Immunity 17(5):561-73. [PubMed: 12433363]  [MGI Ref ID J:93139]

Li T; Ramirez K; Palacios R. 1996. Distinct patterns of Fas cell surface expression during development of T- or B-lymphocyte lineages in normal, scid, and mutant mice lacking or overexpressing p53, bcl-2, or rag-2 genes. Cell Growth Differ 7(1):107-14. [PubMed: 8788039]  [MGI Ref ID J:31364]

Mak TW; Hakem A; McPherson JP; Shehabeldin A; Zablocki E; Migon E; Duncan GS; Bouchard D; Wakeham A; Cheung A; Karaskova J; Sarosi I; Squire J; Marth J; Hakem R. 2000. Brcal required for T cell lineage development but not TCR loci rearrangement. Nat Immunol 1(1):77-82. [PubMed: 10881179]  [MGI Ref ID J:63282]

Maraskovsky E; O'Reilly LA; Teepe M; Corcoran LM; Peschon JJ; Strasser A. 1997. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. Cell 89(7):1011-9. [PubMed: 9215624]  [MGI Ref ID J:41239]

Mastache EF; Lindroth K; Fernandez C; Gonzalez-Fernandez A. 2006. Somatic hypermutation of Ig genes is affected differently by failures in apoptosis caused by disruption of Fas (lpr mutation) or by overexpression of Bcl-2. Scand J Immunol 63(6):420-9. [PubMed: 16764695]  [MGI Ref ID J:129290]

McPherson JP; Hande MP; Poonepalli A; Lemmers B; Zablocki E; Migon E; Shehabeldin A; Porras A; Karaskova J; Vukovic B; Squire J; Hakem R. 2006. A role for Brca1 in chromosome end maintenance. Hum Mol Genet 15(6):831-8. [PubMed: 16446310]  [MGI Ref ID J:106759]

McPherson JP; Lemmers B; Hirao A; Hakem A; Abraham J; Migon E; Matysiak-Zablocki E; Tamblyn L; Sanchez-Sweatman O; Khokha R; Squire J; Hande MP; Mak TW; Hakem R. 2004. Collaboration of Brca1 and Chk2 in tumorigenesis. Genes Dev 18(10):1144-53. [PubMed: 15131084]  [MGI Ref ID J:90512]

Meade J; Tybulewicz VL; Turner M. 2004. The tyrosine kinase Syk is required for light chain isotype exclusion but dispensable for the negative selection of B cells. Eur J Immunol 34(4):1102-10. [PubMed: 15048721]  [MGI Ref ID J:131486]

Melichar HJ; Narayan K; Der SD; Hiraoka Y; Gardiol N; Jeannet G; Held W; Chambers CA; Kang J. 2007. Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13. Science 315(5809):230-3. [PubMed: 17218525]  [MGI Ref ID J:117301]

Newton K; Harris AW; Bath ML; Smith KG; Strasser A. 1998. A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J 17(3):706-18. [PubMed: 9450996]  [MGI Ref ID J:110608]

Newton K; Strasser A. 2000. Ionizing radiation and chemotherapeutic drugs induce apoptosis in lymphocytes in the absence of Fas or FADD/MORT1 signaling. Implications for cancer therapy. J Exp Med 191(1):195-200. [PubMed: 10620618]  [MGI Ref ID J:59250]

O'Reilly LA; Harris AW; Strasser A. 1997. bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors. Int Immunol 9(9):1291-301. [PubMed: 9310832]  [MGI Ref ID J:93122]

O'Reilly LA; Harris AW; Tarlinton DM; Corcoran LM; Strasser A. 1997. Expression of a bcl-2 transgene reduces proliferation and slows turnover of developing B lymphocytes in vivo. J Immunol 159(5):2301-11. [PubMed: 9278319]  [MGI Ref ID J:93123]

Owens BM; Hawley TS; Spain LM; Kerkel KA; Hawley RG. 2006. TLX1/HOX11-mediated disruption of primary thymocyte differentiation prior to the CD4+CD8+ double-positive stage. Br J Haematol 132(2):216-29. [PubMed: 16398656]  [MGI Ref ID J:105116]

Priatel JJ; Chen X; Dhanji S; Abraham N; Teh HS. 2006. RasGRP1 transmits prodifferentiation TCR signaling that is crucial for CD4 T cell development. J Immunol 177(3):1470-80. [PubMed: 16849453]  [MGI Ref ID J:137980]

Rietz C; Screpanti V; Brenden N; Bohme J; Fernandez C. 2003. Overexpression of bcl-2 in T cells affects insulitis in the nonobese diabetic mouse. Scand J Immunol 57(4):342-9. [PubMed: 12662297]  [MGI Ref ID J:131889]

Rietz C; Screpanti V; Brenden N; Fernandez C. 2001. Neonatal pattern of V(H) gene utilization in nonobese diabetic mice does not correlate with development of insulitis. Scand J Immunol 54(5):470-6. [PubMed: 11696198]  [MGI Ref ID J:133860]

Rolle CE; Carrio R; Malek TR. 2008. Modeling the CD8+ T effector to memory transition in adoptive T-cell antitumor immunotherapy. Cancer Res 68(8):2984-92. [PubMed: 18413768]  [MGI Ref ID J:133959]

Shi M; Lin TH; Appell KC; Berg LJ. 2008. Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. Immunity 28(6):763-73. [PubMed: 18549798]  [MGI Ref ID J:137735]

Strasser A; Harris AW; Huang DC; Krammer PH; Cory S. 1995. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J 14(24):6136-47. [PubMed: 8557033]  [MGI Ref ID J:31382]

Strasser A; Harris AW; Vaux DL; Webb E; Bath ML; Adams JM; Cory S. 1990. Abnormalities of the immune system induced by dysregulated bcl-2 expression in transgenic mice. Curr Top Microbiol Immunol 166:175-81. [PubMed: 2073796]  [MGI Ref ID J:93111]

Strasser A; Harris AW; von Boehmer H; Cory S. 1994. Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene. Proc Natl Acad Sci U S A 91(4):1376-80. [PubMed: 8108419]  [MGI Ref ID J:16947]

Tan JT; Dudl E; LeRoy E; Murray R; Sprent J; Weinberg KI; Surh CD. 2001. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 98(15):8732-7. [PubMed: 11447288]  [MGI Ref ID J:93058]

Wilkinson B; Kaye J. 2001. Requirement for sustained MAPK signaling in both CD4 and CD8 lineage commitment: a threshold model. Cell Immunol 211(2):86-95. [PubMed: 11591112]  [MGI Ref ID J:115623]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain is maintained by mating hemizygous mice with C57BL/6J mice or wildtype siblings. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. 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
	Noncarrier
	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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Fax: 207.288.6150
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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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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.