B6.129S1/Sv-Bcl2l11^tm1.1Ast/Kieg

Status	Available to order
EMMA ID	EM:00602
International strain name	B6.129S1/Sv-Bcl2l11^tm1.1Ast/Kieg
Alternative name	bim-/-
Strain type	Targeted Mutant Strains : Knock-out
Allele/Transgene symbol	Bcl2l11^tm1.1Ast,
Gene/Transgene symbol	Bcl2l11

Information from provider

Provider	Andreas Strasser
Provider affiliation	Department of Medicine, Clinical Immunology and Allergy
Genetic information	In the targeting vector, prepared from 129/SvJ DNA, the 110 bp BH3-containing exon is replaced by the PGKneo expression cassette, flanked by loxP sites. Splicing of the remaining Bcl2l11 (bim) exons will produce a frameshift, which introduces a stop codon 12 bp downstream. Linearized targeting vector (30 mg) was electroporated into W9.5 ES cells. Hind III-digested DNA from 133 G418-resistant colonies was screened by Southern blotting with a 3-kb external probe (1.7 kb + 1.3 kb Bgl II fragments), for the 8-kb Hind III fragment. Two independent ES clones bearing a single targeted copy of the Bcl2l11 locus were microinjected into C57BL/6 blastocysts. Chimeric agouti-colored offspring were backcrossed to C57BL/6 mice or C57BL/6 cre recombinase-deleter mice.
Phenotypic information	Elevated leukocyte levels. Perturbed thymic T cell development. With age, Bcl2l11 (bim) deficiency leads to progressive lymphadenopathy and systemic autoimmune disease with elevated Ig levels, and often with enlarged spleen. Many older mice develop kidney disease due to immune complexes. Some of the bim-/- female mice have imperforated vagina and the bim-/- females that do get offsprings are bad mothers. Therefore female bim -/+ are used for breeding.
Breeding history	Bcl2l11-deficient mice (266/266 del) were backcrossed more than 12 generations to C57BL/6 background and then bred by brother x sister mating.
References	Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells.;Enders Anselm, Bouillet Philippe, Puthalakath Hamsa, Xu Yuekang, Tarlinton David M, Strasser Andreas, ;2003;The Journal of experimental medicine;198;1119-26; 14517273 BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes.;Bouillet Philippe, Purton Jared F, Godfrey Dale I, Zhang Li-Chen, Coultas Leigh, Puthalakath Hamsa, Pellegrini Marc, Cory Suzanne, Adams Jerry M, Strasser Andreas, ;2002;Nature;415;922-6; 11859372 Degenerative disorders caused by Bcl-2 deficiency prevented by loss of its BH3-only antagonist Bim.;Bouillet P, Cory S, Zhang L C, Strasser A, Adams J M, ;2001;Developmental cell;1;645-53; 11709185 Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis.;Putcha G V, Moulder K L, Golden J P, Bouillet P, Adams J A, Strasser A, Johnson E M, ;2001;Neuron;29;615-28; 11301022 Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity.;Bouillet P, Metcalf D, Huang D C, Tarlinton D M, Kay T W, Köntgen F, Adams J M, Strasser A, ;1999;Science (New York, N.Y.);286;1735-8; 10576740

Information from EMMA

Archiving centre	Karolinska Institutet, Stockholm, Sweden

Disease and phenotype information

MGI phenotypes (allele matching)

increased leukocyte cell number / MGI
increased spleen weight / MGI
immune system phenotype / MGI
vasculitis / MGI
premature death / MGI
increased IgG level / MGI
increased IgM level / MGI
increased IgA level / MGI
glomerulonephritis / MGI
abnormal lymphocyte physiology / MGI
increased susceptibility to autoimmune disorder / MGI
increased B cell number / MGI
decreased T cell apoptosis / MGI
increased CD4-positive, alpha beta T cell number / MGI
increased CD8-positive, alpha-beta T cell number / MGI
increased splenocyte number / MGI
abnormal sympathetic neuron morphology / MGI
abnormal B cell morphology / MGI
increased regulatory T cell number / MGI
abnormal response to infection / MGI
abnormal NK cell morphology / MGI
abnormal leukopoiesis / MGI
decreased apoptosis / MGI
increased NK cell number / MGI
increased transitional stage B cell number / MGI
increased mature B cell number / MGI
increased immature B cell number / MGI
decreased B cell apoptosis / MGI
decreased physiological sensitivity to xenobiotic / MGI
abnormal CD8-positive, alpha-beta T cell physiology / MGI
hematopoietic system phenotype / MGI
abnormal involution of the mammary gland / MGI
abnormal CD4-positive, alpha beta T cell number / MGI
abnormal splenic cell ratio / MGI
increased monocyte cell number / MGI
increased granulocyte number / MGI
abnormal spleen morphology / MGI
enlarged spleen / MGI
spleen hyperplasia / MGI
increased inflammatory response / MGI
abnormal kidney morphology / MGI
abnormal plasma cell morphology / MGI
dilated renal tubules / MGI
thrombocytopenia / MGI
nervous system phenotype / MGI
increased autoantibody level / MGI
increased anti-double stranded DNA antibody level / MGI
increased anti-single stranded DNA antibody level / MGI
increased anti-nuclear antigen antibody level / MGI
increased anti-histone antibody level / MGI
increased T cell number / MGI
increased double-negative T cell number / MGI
decreased double-positive T cell number / MGI
abnormal B cell proliferation / MGI
abnormal renal glomerulus morphology / MGI
increased blood urea nitrogen level / MGI
increased follicular B cell number / MGI
increased marginal zone B cell number / MGI
embryonic lethality during organogenesis, incomplete penetrance / MGI
abnormal renal glomerulus basement membrane morphology / MGI
expanded mesangial matrix / MGI
increased renal glomerulus apoptosis / MGI
renal cast / MGI
glomerular crescent / MGI
decreased lymphocyte cell number / MGI

Literature references

Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells.;Enders Anselm, Bouillet Philippe, Puthalakath Hamsa, Xu Yuekang, Tarlinton David M, Strasser Andreas, ;2003;The Journal of experimental medicine;198;1119-26; 14517273
BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes.;Bouillet Philippe, Purton Jared F, Godfrey Dale I, Zhang Li-Chen, Coultas Leigh, Puthalakath Hamsa, Pellegrini Marc, Cory Suzanne, Adams Jerry M, Strasser Andreas, ;2002;Nature;415;922-6; 11859372
Degenerative disorders caused by Bcl-2 deficiency prevented by loss of its BH3-only antagonist Bim.;Bouillet P, Cory S, Zhang L C, Strasser A, Adams J M, ;2001;Developmental cell;1;645-53; 11709185
Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis.;Putcha G V, Moulder K L, Golden J P, Bouillet P, Adams J A, Strasser A, Johnson E M, ;2001;Neuron;29;615-28; 11301022
Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity.;Bouillet P, Metcalf D, Huang D C, Tarlinton D M, Kay T W, Köntgen F, Adams J M, Strasser A, ;1999;Science (New York, N.Y.);286;1735-8; 10576740

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Availabilities

Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

Frozen embryos. Delivered in 4 weeks (after paperwork in place). €1740^*
Rederivation of mice from frozen stock, delivery time available upon request . €3880^*

Due to the dynamic nature of our processes strain availability may change at short notice. The local repository manager will advise you in these circumstances.

^* In addition users have to cover all the shipping costs (including the cost for returning dry-shippers, where applicable).

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Practical information

Genotyping protocol

Example health report
(Current health report will be provided later)

Material Transfer Agreement (MTA)
For this strain no provider MTA is needed. Distribution is based on the EMMA conditions only.

EMMA conditions
Legally binding conditions for the transfer

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B6.129S1/Sv-Bcl2l11tm1.1Ast/Kieg