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Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Stanley Korsmeyer, Dana-Farber Cancer Institute Appearance
black
Related Genotype: a/aDescription
Mice homozygous for the Bcl2tm1Sjk targeted mutation appear normal at birth; however, growth retardation is evident by one week of age with considerable heterogeneity in weight compared to normal wildtype siblings (30% to 90%). There is some pre-weaning loss. Homozygotes succumb to renal failure as a result of polycystic kidney disease. Hematopoiesis, including lymphocyte differentiation is initially normal but the thymus and spleen decrease in size due to increased apoptosis. The coat color of homozygotes turns grey with the second hair follicle cycle.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Bcl2
003082 129S1/SvImJ-Bcl2tm1Mpin/J View Strains carrying other alleles of Bcl2 (1 strain)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Bcl2tm1Sjk/Bcl2tm1Sjk
involves: 129S2/SvPas * C57BL/6
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:15224)
- the smallest mutants become noticeably ill and die after 1 week of age, however, the onset of morbidity has a wide range (10 days to 10 weeks), although there is a clustering at 2-3 weeks, just prior to weaning
- life span-post-weaning/aging
- premature death (MGI Ref ID J:15224)
- onset of morbidity has a wide range, from 10 days to 10 weeks, with some surviving longer and to at least 19 weeks of age
- growth/size phenotype
- decreased body size (MGI Ref ID J:15224)
- decreased body size is first seen at 1 week of age and varies from mutant to mutant
- cachexia (MGI Ref ID J:15224)
- mutants that become visibly ill are often lethargic, anorectic, wasted, and at times tremulous
- postnatal growth retardation (MGI Ref ID J:15224)
- growth rate slows after puberty
- exhibit immature facial features at 1 week of age
- hearing/vestibular/ear phenotype
- small ears (MGI Ref ID J:15224)
- craniofacial phenotype
- abnormal snout morphology (MGI Ref ID J:15224)
- rounded snout
- short snout (MGI Ref ID J:15224)
- small ears (MGI Ref ID J:15224)
- immune system phenotype
- abnormal CD4-positive T cell morphology (MGI Ref ID J:15224)
- total numbers of CD4+ single positive thymocytes decrease over time
- abnormal CD8-positive T cell morphology (MGI Ref ID J:15224)
- total numbers of CD8+ single positive thymocytes decrease over time
- abnormal immune system organ morphology (MGI Ref ID J:15224)
- exhibit massive cell death in lymphoid organs as mice age, especially the spleen and thymus, resulting in lymphoid organ involution
- abnormal spleen morphology (MGI Ref ID J:15224)
- spleen undergoes massive apoptotic involution with age
- abnormal spleen red pulp morphology (MGI Ref ID J:15224)
- red pulp shows an increase in the proportion of erythroid relative to myeloid lineage cells
- abnormal spleen white pulp morphology (MGI Ref ID J:15224)
- loss of white pulp lymphoid areas with age and illness; many pyknotic and fragmented cells are noted in white pulp
- small spleen (MGI Ref ID J:15224)
- ill mutants exhibit a decrease in spleen size
- abnormal thymus morphology (MGI Ref ID J:15224)
- exhibit widespread apoptosis in thymus as mutants age and become ill
- small thymus (MGI Ref ID J:15224)
- ill mutants exhibit a decrease in thymus size, with increased apoptosis in both cortex and medulla
- abnormal thymus involution (MGI Ref ID J:15224)
- exhibit involution of thymus with aging and illness
- decreased lymphocyte cell number (MGI Ref ID J:15224)
- the percent of lymphocytes and absolute lymphocyte count are decreased in the peripheral blood of ill mutants (lymphopenia)
- decreased B cell number (MGI Ref ID J:15224)
- exhibit a loss of peripheral B cells over time due to increased apoptosis
- decreased T cell number (MGI Ref ID J:15224)
- exhibit a loss of peripheral T cells over time due to increased apoptosis
- decreased double-positive T cell number (MGI Ref ID J:15224)
- loss of CD4+CD8+ double positive thymocytes over time
- increased T cell apoptosis (MGI Ref ID J:15224)
- thymoctyes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type
- increased double-negative T cell number (MGI Ref ID J:15224)
- increase in double negative CD4-CD8- thymocytes over time
- renal/urinary system phenotype
- abnormal kidney morphology (MGI Ref ID J:15224)
- exhibit hyperproliferative interstitial and glomerular epithelial components with increasing age
- kidneys have an abnormally abnundant interstitium that contains many cells with pyknotic nuclei within nests of immature appearing cells
- abnormal renal glomerular capsule (MGI Ref ID J:15224)
- exhibit replacement of the normal flattened epithelium with a cuboidal proximal tubular epithelium and hyperplasia resulting in an immature epithelial crescent crowding the glomerulus, indicating tubular metaplasia of Bowman's epithelium
- abnormal renal tubule morphology (MGI Ref ID J:15224)
- mitotic figures, not usually found in mature kidneys, are seen in the hyperplastic tubular epithelium
- dilated distal convoluted tubules (MGI Ref ID J:15224)
- proximal and distal tubular ectasia (dilation) are apparent by 1 week after birth
- dilated proximal convoluted tubules (MGI Ref ID J:15224)
- proximal and distal tubular ectasia (dilation) are apparent by 1 week after birth
- enlarged kidney (MGI Ref ID J:15224)
- kidneys are either grossly enlarged and cystic or small and pale
- polycystic kidney (MGI Ref ID J:15224)
- develop polycystic kidney disease
- small kidney (MGI Ref ID J:15224)
- kidneys are either small and pale or grossly enlarged and cystic; small kidneys show small cysts
- homeostasis/metabolism phenotype
- increased blood urea nitrogen level (MGI Ref ID J:15224)
- increases with age
- increased circulating creatinine level (MGI Ref ID J:15224)
- increases with age
- pigmentation phenotype
- hypopigmentation (MGI Ref ID J:15224)
- hair turns gray with the second follicle cycle
- hypopigmentation often begins at the nose and proceeds caudally over 3-4 days
- hair shafts still demonstrate the differentially pigmented regions seen in wild-type, however they are markedly lightened throughout
- Fontana-Mason stain shows the presence of melanin in all hairs, suggesting a decrease in dark pigment rather than a loss of melanocytes
- endocrine/exocrine gland phenotype
- abnormal ovarian follicle morphology (MGI Ref ID J:28173)
- numerous aberrantly formed primordial follicles with a single layer of granulosa cells and lacking oocytes
- normal primary, preantral, and antral follicles, containing normal oocytes
- reproductive system phenotype
- abnormal ovarian follicle morphology (MGI Ref ID J:28173)
- numerous aberrantly formed primordial follicles with a single layer of granulosa cells and lacking oocytes
- normal primary, preantral, and antral follicles, containing normal oocytes
- absent oocytes (MGI Ref ID J:28173)
- loss of oocytes in aberrant primordial follicles
- hematopoietic system phenotype
- abnormal CD4-positive T cell morphology (MGI Ref ID J:15224)
- total numbers of CD4+ single positive thymocytes decrease over time
- abnormal CD8-positive T cell morphology (MGI Ref ID J:15224)
- total numbers of CD8+ single positive thymocytes decrease over time
- abnormal spleen morphology (MGI Ref ID J:15224)
- spleen undergoes massive apoptotic involution with age
- abnormal spleen red pulp morphology (MGI Ref ID J:15224)
- red pulp shows an increase in the proportion of erythroid relative to myeloid lineage cells
- abnormal spleen white pulp morphology (MGI Ref ID J:15224)
- loss of white pulp lymphoid areas with age and illness; many pyknotic and fragmented cells are noted in white pulp
- small spleen (MGI Ref ID J:15224)
- ill mutants exhibit a decrease in spleen size
- abnormal thymus involution (MGI Ref ID J:15224)
- exhibit involution of thymus with aging and illness
- abnormal thymus morphology (MGI Ref ID J:15224)
- exhibit widespread apoptosis in thymus as mutants age and become ill
- small thymus (MGI Ref ID J:15224)
- ill mutants exhibit a decrease in thymus size, with increased apoptosis in both cortex and medulla
- decreased lymphocyte cell number (MGI Ref ID J:15224)
- the percent of lymphocytes and absolute lymphocyte count are decreased in the peripheral blood of ill mutants (lymphopenia)
- decreased B cell number (MGI Ref ID J:15224)
- exhibit a loss of peripheral B cells over time due to increased apoptosis
- decreased T cell number (MGI Ref ID J:15224)
- exhibit a loss of peripheral T cells over time due to increased apoptosis
- decreased double-positive T cell number (MGI Ref ID J:15224)
- loss of CD4+CD8+ double positive thymocytes over time
- increased T cell apoptosis (MGI Ref ID J:15224)
- thymoctyes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type
- increased double-negative T cell number (MGI Ref ID J:15224)
- increase in double negative CD4-CD8- thymocytes over time
- cardiovascular system phenotype
- abnormal pericyte morphology (MGI Ref ID J:96232)
- exhibit a decreased number of pericytes in retinas
- abnormal retinal vasculature (MGI Ref ID J:96232)
- exhibit a significant decrease in retinal vascular density compared to wild-type; retinal vasculature contains less cellularity and fewer capillary loops
- exhibit delayed development and remodeling of retinal vasculature and a significant decrease in the number of major arteries, which branch off from near the optic nerve, however hyaloid vessel regression is not affected
- degree and extent of secondary and tertiary branching is compromised in retinal vasculature
- exhibit increased apoptosis and increased proliferation in the developing retinal vasculature
- degree of ischemia-induced retinal neovascularization is reduced, however show a similar sensitivity to hyperoxia-mediated vessel obliteration
- decreased vascular endothelial cell number (MGI Ref ID J:96232)
- exhibit a decreased number of endothelial cells in the retinas
- vision/eye phenotype
- abnormal retinal vasculature (MGI Ref ID J:96232)
- exhibit a significant decrease in retinal vascular density compared to wild-type; retinal vasculature contains less cellularity and fewer capillary loops
- exhibit delayed development and remodeling of retinal vasculature and a significant decrease in the number of major arteries, which branch off from near the optic nerve, however hyaloid vessel regression is not affected
- degree and extent of secondary and tertiary branching is compromised in retinal vasculature
- exhibit increased apoptosis and increased proliferation in the developing retinal vasculature
- degree of ischemia-induced retinal neovascularization is reduced, however show a similar sensitivity to hyperoxia-mediated vessel obliteration
Bcl2tm1Sjk/Bcl2tm1Sjk
B6;129S2-Bcl2tm1Sjk/J
- muscle phenotype
- abnormal muscle fiber morphology (MGI Ref ID J:66494)
- although soleus and tibialis anterior muscles show similar numbers of slow myofibers as in wild-type, the number of fast myofibers is only about 2/3 the number in wild-type
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Bcl2tm1Sjk related
Apoptosis Research
Endogenous Regulators
Cancer Research
Tumor Suppressor Genes
Developmental Biology Research
Growth Defects
Hematological Research
Hematopoietic Defects
Immunology and Inflammation Research
Immunodeficiency
Intracellular Signaling Molecules
Internal/Organ Research
Kidney Defects (polycystic kidney disease)
Spleen Defects
| Allele Symbol | Bcl2tm1Sjk | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Stanley J Korsmeyer | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Bcl-2-; | ||
| Mutation Made By | Stanley Korsmeyer, Dana-Farber Cancer Institute | ||
| Strain of Origin | 129S2/SvPas | ||
| ES Cell Line Name | D3 | ||
| ES Cell Line Strain | 129S2/SvPas | ||
| Gene Symbol and Name | Bcl2, B-cell leukemia/lymphoma 2 | ||
| Chromosome | 1 | ||
| Gene Common Name(s) | AW986256; Bcl-2; C430015F12Rik; D630044D05Rik; D830018M01Rik; RIKEN cDNA C430015F12 gene; RIKEN cDNA D630044D05 gene; RIKEN cDNA D830018M01 gene; expressed sequence AW986256; | ||
| Molecular Note | A 1.1 kb genomic fragment containing all of the coding region of exon 3 was replaced with a neomycin selection cassette. The authors state that no full length or truncated protein was detected in vitro or in vivo (data not shown). [MGI Ref ID J:15224] | ||
Genotyping Protocols
Bcl2tm1Sjk, STD PCR, vers. 1
NEOTD (Generic Neo), STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Veis DJ; Sorenson CM; Shutter JR; Korsmeyer SJ. 1993. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75(2):229-40. [PubMed: 8402909] [MGI Ref ID J:15224]
Adams JM; Cory S. 1998. The Bcl-2 protein family: arbiters of cell survival. Science 281(5381):1322-6. [PubMed: 9735050] [MGI Ref ID J:49588]
Knudson CM; Korsmeyer SJ. 1997. Bcl-2 and Bax function independently to regulate cell death. Nat Genet 16(4):358-63. [PubMed: 9241272] [MGI Ref ID J:42051]
Sorenson CM; Rogers SA; Korsmeyer SJ; Hammerman MR. 1995. Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am J Physiol 268(1 Pt 2):F73-81. [PubMed: 7840250] [MGI Ref ID J:22552]
Bcl2tm1Sjk relatedBackman M; Machon O; Mygland L; van den Bout CJ; Zhong W; Taketo MM; Krauss S. 2005. Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon. Dev Biol 279(1):155-68. [PubMed: 15708565] [MGI Ref ID J:96233]
Chao DT; Linette GP; Boise LH; White LS; Thompson CB; Korsmeyer SJ. 1995. Bcl-XL and Bcl-2 repress a common pathway of cell death. J Exp Med 182(3):821-8. [PubMed: 7650488] [MGI Ref ID J:78583]
Dominov JA; Houlihan-Kawamoto CA; Swap CJ; Miller JB. 2001. Pro- and anti-apoptotic members of the bcl-2 family in skeletal muscle: A distinct role for bcl-2 in later stages of myogenesis Dev Dyn 220(1):18-26. [PubMed: 11146504] [MGI Ref ID J:66494]
Greenlund LJ; Korsmeyer SJ; Johnson EM Jr. 1995. Role of BCL-2 in the survival and function of developing and mature sympathetic neurons. Neuron 15(3):649-61. [PubMed: 7546744] [MGI Ref ID J:119622]
Hochman A; Liang H; Offen D; Melamed E; Sternin H. 2000. Developmental changes in antioxidant enzymes and oxidative damage in kidneys, liver and brain of bcl-2 knockout mice Cell Mol Biol (Noisy-Le-Grand) 46(1):41-52. [PubMed: 10726970] [MGI Ref ID J:61247]
Hochman A; Sternin H; Gorodin S; Korsmeyer S; Ziv I; Melamed E; Offen D. 1998. Enhanced oxidative stress and altered antioxidants in brains of Bcl-2-deficient mice. J Neurochem 71(2):741-8. [PubMed: 9681465] [MGI Ref ID J:111984]
Knudson CM; Korsmeyer SJ. 1997. Bcl-2 and Bax function independently to regulate cell death. Nat Genet 16(4):358-63. [PubMed: 9241272] [MGI Ref ID J:42051]
Kondo S; Oakes MG; Sorenson CM. 2008. Rescue of renal hypoplasia and cystic dysplasia in Bcl-2 -/- mice expressing Bcl-2 in ureteric bud derived epithelia. Dev Dyn 237(9):2450-9. [PubMed: 18729219] [MGI Ref ID J:138802]
Kondo S; Tang Y; Scheef EA; Sheibani N; Sorenson CM. 2008. Attenuation of retinal endothelial cell migration and capillary morphogenesis in the absence of bcl-2. Am J Physiol Cell Physiol 294(6):C1521-30. [PubMed: 18417716] [MGI Ref ID J:136819]
Middleton G; Cox SW; Korsmeyer S; Davies AM. 2000. Differences in bcl-2- and bax-independent function in regulating apoptosis in sensory neuron populations. Eur J Neurosci 12(3):819-27. [PubMed: 10762311] [MGI Ref ID J:63350]
Nishimura EK; Granter SR; Fisher DE. 2005. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307(5710):720-4. [PubMed: 15618488] [MGI Ref ID J:96016]
Ratts VS; Flaws JA; Kolp R; Sorenson CM; Tilly JL. 1995. Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. Endocrinology 136(8):3665-8. [PubMed: 7628407] [MGI Ref ID J:28173]
Snow JW; Abraham N; Ma MC; Bronson SK; Goldsmith MA. 2003. Transgenic bcl-2 is not sufficient to rescue all hematolymphoid defects in STAT5A/5B-deficient mice. Exp Hematol 31(12):1253-8. [PubMed: 14662332] [MGI Ref ID J:115667]
Sorenson CM. 1999. Nuclear localization of beta-catenin and loss of apical brush border actin in cystic tubules of bcl-2 -/- mice. Am J Physiol 276(2 Pt 2):F210-7. [PubMed: 9950951] [MGI Ref ID J:53123]
Sorenson CM; Padanilam BJ; Hammerman MR. 1996. Abnormal postpartum renal development and cystogenesis in the bcl-2 (-/-) mouse. Am J Physiol 271(1 Pt 2):F184-93. [PubMed: 8760259] [MGI Ref ID J:34504]
Sorenson CM; Rogers SA; Korsmeyer SJ; Hammerman MR. 1995. Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am J Physiol 268(1 Pt 2):F73-81. [PubMed: 7840250] [MGI Ref ID J:22552]
Thompson J; Winoto A. 2008. During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain. J Exp Med 205(5):1029-36. [PubMed: 18443228] [MGI Ref ID J:136238]
Wang S; Sorenson CM; Sheibani N. 2005. Attenuation of retinal vascular development and neovascularization during oxygen-induced ischemic retinopathy in Bcl-2-/- mice. Dev Biol 279(1):205-19. [PubMed: 15708569] [MGI Ref ID J:96232]
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]
Zhang N; He YW. 2005. The antiapoptotic protein Bcl-xL is dispensable for the development of effector and memory T lymphocytes. J Immunol 174(11):6967-73. [PubMed: 15905539] [MGI Ref ID J:99012]
Ziehr J; Sheibani N; Sorenson CM. 2004. Alterations in cell-adhesive and migratory properties of proximal tubule and collecting duct cells from bcl-2 -/- mice. Am J Physiol Renal Physiol 287(6):F1154-63. [PubMed: 15292044] [MGI Ref ID J:95643]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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