Phenotypes associated with this allele

• Allele Symbol: Bcl2l11^tm1.1Ast
• Allele Name: targeted mutation 1.1, Andreas Strasser
• Allele ID: MGI:2156498
• Summary: 28 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	B6.129-Bcl2l11^tm1.1Ast/J	MGI:3803619
hm2	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	B6.129S1-Bcl2l11^tm1.1Ast	MGI:3612866
hm3	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	B6.129S1-Bcl2l11^tm1.1Ast/J	MGI:4421203
hm4	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	involves: 129S1/Sv	MGI:3815010
hm5	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	involves: 129S1/Sv * C57BL/6	MGI:2176744
ht6	Bcl2l11^tm1.1Ast/Bcl2l11^+	B6.129S1-Bcl2l11^tm1.1Ast	MGI:4366833
ht7	Bcl2l11^tm1.1Ast/Bcl2l11^+	involves: 129S1/Sv * C57BL/6	MGI:3612854
cn8	Atmin^tm1.1Jhh/Atmin^tm1.1Jhh Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Cd79a^tm1(cre)Reth/Cd79a^+ Tg(IghMyc)22Bri/0	B6.Cg-Bcl2l11^tm1.1Ast Cd79a^tm1(Cre)Reth Atmin^tm1.1Jhh Tg(IghMyc)22Bri	MGI:5755464
cn9	Bcl2l11^tm1.1Ast/Bcl2l11^+ Pten^tm1Hwu/Pten^+ Tg(CD2-icre)4Kio/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca	MGI:3783573
cn10	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Dicer1^tm1Mmk/Dicer1^tm1Mmk Cd79a^tm1(cre)Reth/Cd79a^+	involves: 129S1/Sv * BALB/c	MGI:3797396
cn11	Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Cd79a^tm1(cre)Reth/Cd79a^+	involves: 129S1/Sv * BALB/c * C57BL/6	MGI:5463975
cx12	Bax^tm1Sjk/Bax^tm1Sjk Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	B6.129-Bcl2l11^tm1.1Ast Bax^tm1Sjk	MGI:3612872
cx13	Bcl2^tm1Dlo/Bcl2^tm1Dlo Bcl2l11^tm1.1Ast/Bcl2l11^+	B6.129-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast	MGI:2176747
cx14	Bcl2^tm1Dlo/Bcl2^tm1Dlo Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	B6.129-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast	MGI:2176749
cx15	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Bmf^tm1Rjd/Bmf^tm1Rjd	B6.129S-Bcl2l11^tm1.1Ast Bmf^tm1Rjd	MGI:4421201
cx16	Bcl2l11^tm1.1Ast/Bcl2l11^+ Bmf^tm1Rjd/Bmf^+	B6.129S-Bcl2l11^tm1.1Ast Bmf^tm1Rjd	MGI:4421202
cx17	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Bmf^tm2.1Rjd/Bmf^tm2.1Rjd	B6.129S-Bcl2l11^tm1.1Ast Bmf^tm2.1Rjd	MGI:4421205
cx18	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Bik^tm1Ast/Bik^tm1Ast	B6.Cg-Bcl2l11^tm1.1Ast Bik^tm1Ast	MGI:3612869
cx19	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Fas^lpr/Fas^lpr	B6.Cg-Bcl2l11^tm1.1Ast Fas^lpr	MGI:3800656
cx20	Bcl2^tm1Dlo/Bcl2^tm1Dlo Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast	B6.Cg-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast	MGI:4366842
cx21	Bcl2^tm1Dlo/Bcl2^tm1Dlo Bcl2l11^tm1.1Ast/Bcl2l11^+	B6.Cg-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast	MGI:4366843
cx22	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Gata1^tm1.1Yen/Gata1^tm1.1Yen	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5521638
cx23	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Zbtb1^m1Btlr/Zbtb1^m1Btlr	involves: 129S1/Sv * C3H/HeN * C57BL/6 * C57BL/6J	MGI:5300539
cx24	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Mlf1^tm1Swm/Mlf1^tm1Swm	involves: 129S1/Sv * C57BL/6	MGI:6267420
cx25	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Pmaip1^tm1Ast/Pmaip1^tm1Ast	involves: 129S1/Sv * C57BL/6	MGI:3720170
cx26	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Bnip3l^Gt(XT0573)Wtsi/Bnip3l^Gt(XT0573)Wtsi	involves: 129S1/Sv * C57BL/6	MGI:3803618
cx27	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Mirc14^tm1.2Flv/Mirc14^tm1.2Flv	involves: 129S1/Sv * C57BL/6 * C57BL/6N * FVB/N * SJL	MGI:5529023
cx28	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Il15^tm1Imx/Il15^tm1Imx	involves: C57BL/6	MGI:5562714

Genotype
MGI:3803619

hm1

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: B6.129-Bcl2l11^tm1.1Ast/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hematopoietic system

decreased lymphocyte cell number ( J:137609 )

immune system

decreased lymphocyte cell number ( J:137609 )

Genotype
MGI:3612866

hm2

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: B6.129S1-Bcl2l11^tm1.1Ast

immune system

immune system phenotype ( J:153846 )

N • normal in vitro survival assays with several cytotoxic stimuli on sorted thymocyte and B cell populations

increased spleen weight ( J:153846 )

• increased spleen weight (>2.5 fold)

abnormal leukopoiesis ( J:73316 )

• irradiated mice reconstituted with mutant fetal liver cells have a 2- to 4- fold increase in lymphocyte and myeloid cell numbers compared to controls

increased immature B cell number ( J:133084 )

increased transitional stage B cell number ( J:133084 )

• T1 transitional B cells are insignificantly elevated

• increased T1 transitional B cells in inguinal lymph nodes

increased leukocyte cell number ( J:153846 )

• increased white blood cells numbers (>3 fold)

increased regulatory T cell number ( J:208318 )

• at 6 months

abnormal B cell morphology ( J:133084 )

increased mature B cell number ( J:133084 )

abnormal NK cell morphology ( J:123409 )

• following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells

increased NK cell number ( 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 ( J:73316 )

• survival of mature resting T and B cells in the absence of cytokines is improved compared to wild-type cells

decreased B cell apoptosis ( J:73316 )

• about 10-fold more B cells cultured without cytokines are alive after six days compared to controls

decreased T cell apoptosis ( J:73316 , J:133084 )

• about 10-fold more T cells cultured without cytokines are alive after six days compared to controls (J:73316)

• double positive T cells with increased resistance to the apoptotic effects of dexamethasone (J:133084)

abnormal response to infection ( J:123409 )

• following infection with mouse cytomegalovirus infection, more NK cell survive at day 10 and 14 than in wild-type mice

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:123409 )

• NK cells are more resistant to LY294002-induced apoptosis

cellular

decreased apoptosis ( 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

decreased B cell apoptosis ( J:73316 )

• about 10-fold more B cells cultured without cytokines are alive after six days compared to controls

decreased T cell apoptosis ( J:73316 , J:133084 )

• about 10-fold more T cells cultured without cytokines are alive after six days compared to controls (J:73316)

• double positive T cells with increased resistance to the apoptotic effects of dexamethasone (J:133084)

nervous system

abnormal sympathetic neuron morphology ( J:124044 )

• sympathetic neurons are partially protected from apoptosis induced by the withdrawal of nerve growth factor

hematopoietic system

increased spleen weight ( J:153846 )

• increased spleen weight (>2.5 fold)

abnormal leukopoiesis ( J:73316 )

• irradiated mice reconstituted with mutant fetal liver cells have a 2- to 4- fold increase in lymphocyte and myeloid cell numbers compared to controls

increased leukocyte cell number ( J:153846 )

• increased white blood cells numbers (>3 fold)

increased regulatory T cell number ( J:208318 )

• at 6 months

abnormal B cell morphology ( J:133084 )

increased immature B cell number ( J:133084 )

increased transitional stage B cell number ( J:133084 )

• T1 transitional B cells are insignificantly elevated

• increased T1 transitional B cells in inguinal lymph nodes

increased mature B cell number ( J:133084 )

abnormal NK cell morphology ( J:123409 )

• following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells

increased NK cell number ( 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 ( J:73316 )

• survival of mature resting T and B cells in the absence of cytokines is improved compared to wild-type cells

decreased B cell apoptosis ( J:73316 )

• about 10-fold more B cells cultured without cytokines are alive after six days compared to controls

decreased T cell apoptosis ( J:73316 , J:133084 )

• about 10-fold more T cells cultured without cytokines are alive after six days compared to controls (J:73316)

• double positive T cells with increased resistance to the apoptotic effects of dexamethasone (J:133084)

growth/size/body

increased spleen weight ( J:153846 )

• increased spleen weight (>2.5 fold)

Genotype
MGI:4421203

hm3

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: B6.129S1-Bcl2l11^tm1.1Ast/J

immune system

decreased T cell apoptosis ( J:153652 )

• increased viability of CD4 and CD8 T cells during in vitro culture of T cells purified from spleen and lymph nodes

increased B cell number ( J:153652 )

• a large increase in the number of B cells in the spleen

increased CD4-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD4-positive T cells in the spleen

increased CD8-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD8-positive T cells in the spleen

increased splenocyte number ( J:153652 )

• increased number of splenocytes (>3 fold)

hematopoietic system

decreased T cell apoptosis ( J:153652 )

• increased viability of CD4 and CD8 T cells during in vitro culture of T cells purified from spleen and lymph nodes

increased B cell number ( J:153652 )

• a large increase in the number of B cells in the spleen

increased CD4-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD4-positive T cells in the spleen

increased CD8-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD8-positive T cells in the spleen

increased splenocyte number ( J:153652 )

• increased number of splenocytes (>3 fold)

cellular

decreased T cell apoptosis ( J:153652 )

• increased viability of CD4 and CD8 T cells during in vitro culture of T cells purified from spleen and lymph nodes

Genotype
MGI:3815010

hm4

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: involves: 129S1/Sv

immune system

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type

• in response to cis-diammine-dichloroplatinum II (cisplatin), phorbol 12- myristate 13-acetate (PMA), dexamethasone (Dex), anti-Fas, and UV irradiation

decreased splenocyte apoptosis ( J:266833 )

• almost no loss of cellular viability ex vivo upon cytokine depletion compared with wild-type

increased B cell number ( J:132819 )

• 2- to 4- fold increase in B220+ positive cells

abnormal CD4-positive, alpha-beta T cell number ( J:132819 )

• 2- to 4- fold increase

abnormal splenic cell ratio ( J:132819 )

• increase in the number of HSV-1 specific T cells in the spleen but not lymph nodes after infection

abnormal CD8-positive, alpha-beta T cell physiology ( J:132819 )

• HSV-1 antigen specific CD8+ T cells show nearly complete resistance to cytokine withdrawal induced apoptosis in culture

integument

abnormal involution of the mammary gland ( J:235354 )

♀ • delay in postlactational remodeling of the mammary gland

cellular

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type

• in response to cis-diammine-dichloroplatinum II (cisplatin), phorbol 12- myristate 13-acetate (PMA), dexamethasone (Dex), anti-Fas, and UV irradiation

decreased splenocyte apoptosis ( J:266833 )

• almost no loss of cellular viability ex vivo upon cytokine depletion compared with wild-type

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type

• in response to cis-diammine-dichloroplatinum II (cisplatin), phorbol 12- myristate 13-acetate (PMA), dexamethasone (Dex), anti-Fas, and UV irradiation

abnormal involution of the mammary gland ( J:235354 )

♀ • delay in postlactational remodeling of the mammary gland

hematopoietic system

hematopoietic system phenotype ( J:141545 )

N • unlike in Bnip3l^tm1Ney homozygotes, reticulocytes clearance of mitochondria is normal

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type

• in response to cis-diammine-dichloroplatinum II (cisplatin), phorbol 12- myristate 13-acetate (PMA), dexamethasone (Dex), anti-Fas, and UV irradiation

decreased splenocyte apoptosis ( J:266833 )

• almost no loss of cellular viability ex vivo upon cytokine depletion compared with wild-type

increased B cell number ( J:132819 )

• 2- to 4- fold increase in B220+ positive cells

abnormal CD4-positive, alpha-beta T cell number ( J:132819 )

• 2- to 4- fold increase

abnormal splenic cell ratio ( J:132819 )

• increase in the number of HSV-1 specific T cells in the spleen but not lymph nodes after infection

abnormal CD8-positive, alpha-beta T cell physiology ( J:132819 )

• HSV-1 antigen specific CD8+ T cells show nearly complete resistance to cytokine withdrawal induced apoptosis in culture

Genotype
MGI:2176744

hm5

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

premature death ( J:58641 )

• by 1 year of age 55% of homozygotes are terminally ill with 85% of these developing kidney disease (immune complex glomerulonephritis)

embryonic lethality during organogenesis, incomplete penetrance ( J:58641 )

• Background Sensitivity: about half die before E10; however, this percentage is highly variable and background dependent

immune system

decreased double-positive T cell number ( 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 leukocyte cell number ( 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 granulocyte number ( J:58641 )

• 2- to 4-fold increase

increased B cell number ( J:58641 )

• 2- to 4-fold increase

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased relative to wild-type

increased transitional stage B cell number ( J:132217 )

• higher numbers of T1 and T2 B cells in spleen relative to wild-type

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type and Fas^lpr homozygotes

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type and Fas^lpr homozygotes

increased T cell number ( J:58641 )

• 2- to 4-fold increase involving mostly mature T cells is seen in adult mice

increased double-negative T cell number ( J:58641 )

• 2- to 3-fold increase is seen in adult mice

increased CD4-positive, alpha-beta T cell number ( J:58641 )

• 2- to 3-fold increase in the number of CD4+ T cells is seen in adult mice

increased CD8-positive, alpha-beta T cell number ( J:58641 )

• 2- to 3-fold increase in the number of CD8+ T cells is seen in adult mice

increased monocyte cell number ( J:58641 )

• 2- to 4-fold increase

abnormal plasma cell morphology ( 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 ( J:58641 )

enlarged spleen ( J:58641 )

• in older homozygotes spleen size is increased 5- to 10-fold

spleen hyperplasia ( J:58641 )

• seen in older homozygotes with plasma cells most severely affected

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is higher than wild-type

increased splenocyte number ( J:132217 )

• total number of CD19+ splenocytes is higher than wild-type

• total number of splenocytes is increased relative to wild-type

abnormal lymphocyte physiology ( 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

decreased B cell apoptosis ( J:90963 )

• IL-21 fails to induce apoptosis in LPS-activated B cells as it does in wild-type mice

abnormal B cell proliferation ( J:90963 )

• 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

increased IgA level ( J:58641 )

• elevated about 3-fold at 6 to 12 months of age

increased IgG level ( J:58641 )

• elevated about 10-fold at 6 to 12 months of age

increased IgM level ( J:58641 )

• elevated about 3-fold at 6 to 12 months of age

increased susceptibility to autoimmune disorder ( J:58641 )

• older homozygotes develop lymphadenopathy

increased autoantibody level ( J:132217 )

• total anti-IgM antibody levels are increased compared to wild-type

increased anti-nuclear antigen antibody level ( J:132217 )

• anti-nuclear antibodies are increased compared to wild-type

increased anti-double stranded DNA antibody level ( J:132217 )

• anti-SsDNA IgM and IgG antibodies are increased compared to wild-type

increased anti-histone antibody level ( J:132217 )

• increased compared to wild-type

increased anti-single stranded DNA antibody level ( J:132217 )

• anti-ssDNA IgM and IgG antibodies are increased compared to wild-type

increased inflammatory response ( J:58641 )

glomerulonephritis ( J:58641 )

• by 1 year of about 85% of terminally ill homozygotes have immune complex glomerulonephritis

renal/urinary system

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type

abnormal kidney morphology ( J:132217 )

• number of macrophages surrounding glomeruli is increased compared to wild-type and Fas^lpr homozygotes

• number of macrophages surrounding glomeruli is increased compared to wild-type, and is similar to that in double mutants

abnormal renal glomerulus basement membrane morphology ( J:132217 )

• IgG deposits mainly localized to glomerular basement membrane are increased relative to wild-type

abnormal renal glomerulus morphology ( J:58641 )

• hypercellularity is seen in homozygotes with kidney disease

glomerulonephritis ( J:58641 )

• by 1 year of about 85% of terminally ill homozygotes have immune complex glomerulonephritis

expanded mesangial matrix ( J:58641 )

glomerular crescent ( J:58641 )

• proliferation of capsular epithelial cells is seen in homozygotes with kidney disease

renal glomerular immunoglobulin deposits ( J:58641 )

dilated renal tubule ( J:58641 )

• eosinophilic deposits are seen in dilated renal tubules in homozygotes with kidney disease

renal cast ( J:58641 )

• dilated renal tubules contain eosinophilic casts

homeostasis/metabolism

increased blood urea nitrogen level ( J:58641 )

nervous system

nervous system phenotype ( J:127640 )

N • unlike mice homozygous for Bbc3^tm1Ast neuron sensitivity to oxidative stressor induced apoptosis is similar to controls

hematopoietic system

decreased double-positive T cell number ( 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

thrombocytopenia ( J:58641 )

• platelet count is reduced to about 1/2 of wild-type; however, megakaryocyte numbers are normal

increased leukocyte cell number ( 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 granulocyte number ( J:58641 )

• 2- to 4-fold increase

increased B cell number ( J:58641 )

• 2- to 4-fold increase

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased relative to wild-type

increased transitional stage B cell number ( J:132217 )

• higher numbers of T1 and T2 B cells in spleen relative to wild-type

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type and Fas^lpr homozygotes

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type and Fas^lpr homozygotes

increased T cell number ( J:58641 )

• 2- to 4-fold increase involving mostly mature T cells is seen in adult mice

increased double-negative T cell number ( J:58641 )

• 2- to 3-fold increase is seen in adult mice

increased CD4-positive, alpha-beta T cell number ( J:58641 )

• 2- to 3-fold increase in the number of CD4+ T cells is seen in adult mice

increased CD8-positive, alpha-beta T cell number ( J:58641 )

• 2- to 3-fold increase in the number of CD8+ T cells is seen in adult mice

increased monocyte cell number ( J:58641 )

• 2- to 4-fold increase

abnormal plasma cell morphology ( 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 ( J:58641 )

enlarged spleen ( J:58641 )

• in older homozygotes spleen size is increased 5- to 10-fold

spleen hyperplasia ( J:58641 )

• seen in older homozygotes with plasma cells most severely affected

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is higher than wild-type

increased splenocyte number ( J:132217 )

• total number of CD19+ splenocytes is higher than wild-type

• total number of splenocytes is increased relative to wild-type

abnormal lymphocyte physiology ( 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

decreased B cell apoptosis ( J:90963 )

• IL-21 fails to induce apoptosis in LPS-activated B cells as it does in wild-type mice

abnormal B cell proliferation ( J:90963 )

• 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

increased IgA level ( J:58641 )

• elevated about 3-fold at 6 to 12 months of age

increased IgG level ( J:58641 )

• elevated about 10-fold at 6 to 12 months of age

increased IgM level ( J:58641 )

• elevated about 3-fold at 6 to 12 months of age

cardiovascular system

vascular inflammation ( J:58641 )

• about 20% of terminally ill homozygotes show signs of vasculitis or cardiac infarction

cellular

decreased B cell apoptosis ( J:90963 )

• IL-21 fails to induce apoptosis in LPS-activated B cells as it does in wild-type mice

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type

abnormal B cell proliferation ( J:90963 )

• 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

growth/size/body

enlarged spleen ( J:58641 )

• in older homozygotes spleen size is increased 5- to 10-fold

spleen hyperplasia ( J:58641 )

• seen in older homozygotes with plasma cells most severely affected

Genotype
MGI:4366833

ht6

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11⁺
• Genetic Background: B6.129S1-Bcl2l11^tm1.1Ast

hematopoietic system

increased spleen weight ( J:153846 )

• increase in spleen weight (<2 fold)

increased leukocyte cell number ( J:153846 )

• increased white blood cells numbers (<1.5 fold)

immune system

immune system phenotype ( J:153846 )

N • normal in vitro survival assays with several cytotoxic stimuli on sorted thymocyte and B cell populations

increased spleen weight ( J:153846 )

• increase in spleen weight (<2 fold)

increased leukocyte cell number ( J:153846 )

• increased white blood cells numbers (<1.5 fold)

growth/size/body

increased spleen weight ( J:153846 )

• increase in spleen weight (<2 fold)

Genotype
MGI:3612854

ht7

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

premature death ( J:58641 )

• by 1 year of age 35% of heterozygotes are terminally ill

immune system

abnormal lymphocyte physiology ( 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 ( J:58641 )

• increased at 6 to 12 months of age but less than in homozygous mice

increased IgG level ( J:58641 )

• increased at 6 to 12 months of age but less than in homozygous mice

increased IgM level ( J:58641 )

• increased at 6 to 12 months of age but less than in homozygous mice

increased susceptibility to autoimmune disorder ( J:58641 )

• older heterozygotes develop lymphadenopathy

glomerulonephritis ( J:58641 )

• by 1 year of about 85% of terminally ill heterozygotes have immune complex glomerulonephritis

renal/urinary system

glomerulonephritis ( J:58641 )

• by 1 year of about 85% of terminally ill heterozygotes have immune complex glomerulonephritis

renal glomerular immunoglobulin deposits ( J:58641 )

cardiovascular system

vascular inflammation ( J:58641 )

• about 20% of terminally ill heterozygotes show signs of vasculitis or cardiac infarction

hematopoietic system

abnormal lymphocyte physiology ( 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 ( J:58641 )

• increased at 6 to 12 months of age but less than in homozygous mice

increased IgG level ( J:58641 )

• increased at 6 to 12 months of age but less than in homozygous mice

increased IgM level ( J:58641 )

• increased at 6 to 12 months of age but less than in homozygous mice

Genotype
MGI:5755464

cn8

• Allelic Composition: Atmin^tm1.1Jhh/Atmin^tm1.1Jhh; Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Cd79a^tm1(cre)Reth/Cd79a⁺; Tg(IghMyc)22Bri/0
• Genetic Background: B6.Cg-Bcl2l11^tm1.1Ast Cd79a^tm1(Cre)Reth Atmin^tm1.1Jhh Tg(IghMyc)22Bri

neoplasm

increased lymphoma incidence ( J:230105 )

• compared with Tg(IghMyc)22Bri mice

Genotype
MGI:3783573

cn9

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11⁺; Pten^tm1Hwu/Pten⁺; Tg(CD2-icre)4Kio/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca

immune system

increased germinal center B cell number ( J:133215 )

• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

abnormal T cell number ( J:133215 )

• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

hematopoietic system

increased germinal center B cell number ( J:133215 )

• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

abnormal T cell number ( J:133215 )

• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

Genotype
MGI:3797396

cn10

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Dicer1^tm1Mmk/Dicer1^tm1Mmk; Cd79a^tm1(cre)Reth/Cd79a⁺
• Genetic Background: involves: 129S1/Sv * BALB/c

immune system

decreased B cell number ( J:135783 )

• while B cell numbers are increased relative to in Cd79a^tm1(cre)Reth/Cd79a⁺ Bcl2l11^tm1.1Ast/Bcl2l11⁺ Dicer1^tm1Mmk/Dicer1^tm1Mmk mice, numbers are still lower than in wild-type mice

decreased mature B cell number ( J:135783 )

hematopoietic system

decreased B cell number ( J:135783 )

• while B cell numbers are increased relative to in Cd79a^tm1(cre)Reth/Cd79a⁺ Bcl2l11^tm1.1Ast/Bcl2l11⁺ Dicer1^tm1Mmk/Dicer1^tm1Mmk mice, numbers are still lower than in wild-type mice

decreased mature B cell number ( J:135783 )

Genotype
MGI:5463975

cn11

• Allelic Composition: Atmin^tm1.2Jhh/Atmin^tm1.2Jhh; Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Cd79a^tm1(cre)Reth/Cd79a⁺
• Genetic Background: involves: 129S1/Sv * BALB/c * C57BL/6

immune system

immune system phenotype ( J:191832 )

N • B cell development is rescued compared with Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

enlarged spleen ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased spleen weight ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased B cell number ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased immature B cell number ( J:191832 )

• compared with Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased pre-B cell number ( J:191832 )

• compared with Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

hematopoietic system

enlarged spleen ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased spleen weight ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased B cell number ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased immature B cell number ( J:191832 )

• compared with Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased pre-B cell number ( J:191832 )

• compared with Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

growth/size/body

enlarged spleen ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

increased spleen weight ( J:191832 )

• compared with control and Atmin^tm1.2Jhh/Atmin^tm1.2Jhh Cd79a^tm1(cre)Reth/Cd79a⁺ mice

Genotype
MGI:3612872

cx12

• Allelic Composition: Bax^tm1Sjk/Bax^tm1Sjk; Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: B6.129-Bcl2l11^tm1.1Ast Bax^tm1Sjk

reproductive system

azoospermia ( J:103605 )

♂

arrest of male meiosis ( J:103605 )

♂ • arrests before the completion of meiosis in the preleptotene spermatocyte stage identical to Bax^tm1Sjk homozygotes

abnormal seminiferous tubule epithelium morphology ( J:103605 )

♂ • the epithelium is grossly dysmorphic

small seminiferous tubules ( J:103605 )

♂ • tubule diameter is decreased and no spermatids are seen

male infertility ( J:103605 )

♂ • males but not females are sterile

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:103605 )

♂ • the epithelium is grossly dysmorphic

small seminiferous tubules ( J:103605 )

♂ • tubule diameter is decreased and no spermatids are seen

cellular

azoospermia ( J:103605 )

♂

arrest of male meiosis ( J:103605 )

♂ • arrests before the completion of meiosis in the preleptotene spermatocyte stage identical to Bax^tm1Sjk homozygotes

Genotype
MGI:2176747

cx13

• Allelic Composition: Bcl2^tm1Dlo/Bcl2^tm1Dlo; Bcl2l11^tm1.1Ast/Bcl2l11⁺
• Genetic Background: B6.129-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast

mortality/aging

mortality/aging ( J:73316 )

N • mice are healthy through at least 6 months of age

pigmentation

abnormal coat/hair pigmentation ( J:73316 )

• coat color becomes gray at 5 to 7 weeks of age during completion of the second hair follicle cycle

• from the second follicle cycle on all newly grown hairs lack melanin and when an area is shaved the coat appears white suggesting the gray color is a result of unshed hairs from the first cycle

abnormal hair follicle melanocyte morphology ( J:73316 )

• by 5 to 7 weeks of age melanocytes are lost from the hair follicles

absent hair follicle melanin granules ( J:73316 )

• absent from hair starting at the second hair follicle cycle

diluted coat color ( J:73316 )

• coat colors become grey after two hair follicle cycles

• in areas where skin is shaved, hair comes back completely white

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:73316 )

N • ear length is normal

immune system

abnormal lymphocyte physiology ( J:73316 )

• survival of mature resting T and B cells in the absence of cytokines is improved compared to cells from mice homozygous for Bcl2^tm1Dlo alone

increased T cell apoptosis ( J:73316 )

• culturing with IL-7 only partially rescues T cells from apoptosis

renal/urinary system

renal/urinary system phenotype ( J:73316 )

N • mice do not develop polycystic kidney disease

integument

abnormal coat/hair pigmentation ( J:73316 )

• coat color becomes gray at 5 to 7 weeks of age during completion of the second hair follicle cycle

• from the second follicle cycle on all newly grown hairs lack melanin and when an area is shaved the coat appears white suggesting the gray color is a result of unshed hairs from the first cycle

abnormal hair follicle melanocyte morphology ( J:73316 )

• by 5 to 7 weeks of age melanocytes are lost from the hair follicles

absent hair follicle melanin granules ( J:73316 )

• absent from hair starting at the second hair follicle cycle

diluted coat color ( J:73316 )

• coat colors become grey after two hair follicle cycles

• in areas where skin is shaved, hair comes back completely white

cellular

increased T cell apoptosis ( J:73316 )

• culturing with IL-7 only partially rescues T cells from apoptosis

hematopoietic system

abnormal lymphocyte physiology ( J:73316 )

• survival of mature resting T and B cells in the absence of cytokines is improved compared to cells from mice homozygous for Bcl2^tm1Dlo alone

increased T cell apoptosis ( J:73316 )

• culturing with IL-7 only partially rescues T cells from apoptosis

Genotype
MGI:2176749

cx14

• Allelic Composition: Bcl2^tm1Dlo/Bcl2^tm1Dlo; Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: B6.129-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast

mortality/aging

mortality/aging ( J:73316 )

N • mice are healthy through at least 6 months of age

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:73316 )

N • ear length is normal

immune system

abnormal leukopoiesis ( J:73316 )

• irradiated mice reconstituted with mutant fetal liver cells have an increase in lymphocyte and myeloid cell numbers compared to controls

abnormal lymphocyte physiology ( J:73316 )

• survival of mature resting T and B cells in the absence of cytokines is improved compared to cells from mice homozygous for Bcl2^tm1Dlo alone and cells from wild-type mice

decreased B cell apoptosis ( J:73316 )

• about 10-fold more B cells cultured without cytokines are alive after six days compared to controls

increased T cell apoptosis ( J:73316 )

• culturing with IL-7 only partially rescues T cells from apoptosis over a 6 day period

renal/urinary system

renal/urinary system phenotype ( J:73316 )

N • mice do not develop polycystic kidney disease

hematopoietic system

abnormal leukopoiesis ( J:73316 )

• irradiated mice reconstituted with mutant fetal liver cells have an increase in lymphocyte and myeloid cell numbers compared to controls

abnormal lymphocyte physiology ( J:73316 )

• survival of mature resting T and B cells in the absence of cytokines is improved compared to cells from mice homozygous for Bcl2^tm1Dlo alone and cells from wild-type mice

decreased B cell apoptosis ( J:73316 )

• about 10-fold more B cells cultured without cytokines are alive after six days compared to controls

increased T cell apoptosis ( J:73316 )

• culturing with IL-7 only partially rescues T cells from apoptosis over a 6 day period

integument

integument phenotype ( J:73316 )

N • coat color is normal

cellular

decreased B cell apoptosis ( J:73316 )

• about 10-fold more B cells cultured without cytokines are alive after six days compared to controls

increased T cell apoptosis ( J:73316 )

• culturing with IL-7 only partially rescues T cells from apoptosis over a 6 day period

Genotype
MGI:4421201

cx15

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Bmf^tm1Rjd/Bmf^tm1Rjd
• Genetic Background: B6.129S-Bcl2l11^tm1.1Ast Bmf^tm1Rjd

mortality/aging

postnatal lethality, incomplete penetrance ( J:153652 )

• reduced number of homozygous mice generated from intercross of the double heterozygous compared with the expected Mendelian inheritance

growth/size/body

decreased body weight ( J:153652 )

• decreased body weight at 6 weeks old

limbs/digits/tail

interdigital webbing ( J:153652 )

• persistence of interdigital tissue on both the front and rear paws

reproductive system

vagina atresia ( J:153652 )

♀ • imperforate vagina in female mice

hydrometrocolpos ( J:153652 )

♀ • hydrometrocolpos in female mice

immune system

decreased T cell apoptosis ( J:153652 )

• increased viability of CD4-positive and CD8-positive T cells during in vitro culture of T cells purified from spleen and lymph nodes

increased thymocyte number ( J:153652 )

• increased numbers of CD4-positive, CD8-positive, and CD4/CD8 double-positive thymocytes

increased B cell number ( J:153652 )

• a large increase in the number of B cells in the spleen

increased CD4-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD4-positive T cells in the spleen

increased CD8-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD8-positive T cells in the spleen

increased splenocyte number ( J:153652 )

• a larger increased number of splenocytes (>5 fold)

hematopoietic system

decreased T cell apoptosis ( J:153652 )

• increased viability of CD4-positive and CD8-positive T cells during in vitro culture of T cells purified from spleen and lymph nodes

increased thymocyte number ( J:153652 )

• increased numbers of CD4-positive, CD8-positive, and CD4/CD8 double-positive thymocytes

increased B cell number ( J:153652 )

• a large increase in the number of B cells in the spleen

increased CD4-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD4-positive T cells in the spleen

increased CD8-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD8-positive T cells in the spleen

increased splenocyte number ( J:153652 )

• a larger increased number of splenocytes (>5 fold)

cellular

decreased T cell apoptosis ( J:153652 )

• increased viability of CD4-positive and CD8-positive T cells during in vitro culture of T cells purified from spleen and lymph nodes

endocrine/exocrine glands

increased thymocyte number ( J:153652 )

• increased numbers of CD4-positive, CD8-positive, and CD4/CD8 double-positive thymocytes

Genotype
MGI:4421202

cx16

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11⁺; Bmf^tm1Rjd/Bmf⁺
• Genetic Background: B6.129S-Bcl2l11^tm1.1Ast Bmf^tm1Rjd

growth/size/body

decreased body weight ( J:153652 )

• decreased body weight at 6 weeks old

Genotype
MGI:4421205

cx17

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Bmf^tm2.1Rjd/Bmf^tm2.1Rjd
• Genetic Background: B6.129S-Bcl2l11^tm1.1Ast Bmf^tm2.1Rjd

hematopoietic system

increased B cell number ( J:153652 )

• a large increase in the number of B cells in the spleen

increased CD4-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD4-positive T cells in the spleen

increased CD8-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD8-positive T cells in the spleen

increased splenocyte number ( J:153652 )

• increased numbers of splenocytes (about 2.5 fold) compared with the wild type

immune system

increased B cell number ( J:153652 )

• a large increase in the number of B cells in the spleen

increased CD4-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD4-positive T cells in the spleen

increased CD8-positive, alpha-beta T cell number ( J:153652 )

• a large increase in the number of CD8-positive T cells in the spleen

increased splenocyte number ( J:153652 )

• increased numbers of splenocytes (about 2.5 fold) compared with the wild type

Genotype
MGI:3612869

cx18

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Bik^tm1Ast/Bik^tm1Ast
• Genetic Background: B6.Cg-Bcl2l11^tm1.1Ast Bik^tm1Ast

growth/size/body

decreased body weight ( J:103605 )

• seen in about 50% of mice

enlarged spleen ( J:103605 )

• increase in size is similar to mice homozygous for Bcl2l11^tm1.1Ast alone

reproductive system

multinucleated giant male germ cells ( J:103605 )

♂

abnormal seminiferous tubule morphology ( J:103605 )

♂ • variable abnormalities are seen including vacuolation, multi-nucleate syncytia, accumulation of spermatocytes, and apparent reduction in tubular cellularity, diameter, and lumen size

♂ • the spermatogonia layer is thicker than in wild-type being up to 3 cell layers thick

decreased testis weight ( J:103605 )

♂ • testes weight is reduced at P21 and in adults testes weigh about 60% that of wild-type; however serum concentrations of inhibin and follicle stimulating hormone are normal

abnormal spermatogenesis ( J:103605 )

♂ • at P15 the number of germ cells in the testis is increased and these are mostly c-Kit+ early germ cells, but in adult males the number of germ cells is decreased by up to 10-fold compared to wild-type

♂ • in adult males the proportion of early germ cells is increased up to 10-fold compared to controls; however the absolute number is similar to controls

azoospermia ( J:103605 )

♂

arrest of male meiosis ( J:103605 )

♂ • arrest is later than in Bax^tm1Sjk homozygotes as some round spermatids are present but no elongating spermatids are seen

male infertility ( J:103605 )

♂ • males but not females are sterile

immune system

enlarged spleen ( J:103605 )

• increase in size is similar to mice homozygous for Bcl2l11^tm1.1Ast alone

abnormal B cell differentiation ( J:103605 )

• in the bone marrow the pro/pre-B and immature B cell populations are reduced and the population of mature b cells is increased similar to mice homozygous for Bcl2l11^tm1.1Ast alone

decreased immature B cell number ( J:103605 )

• in bone marrow

decreased pro-B cell number ( J:103605 )

• in bone marrow

abnormal T cell differentiation ( J:103605 )

• abnormalities in T cell development in the thymus (decrease in pre-T cells and increase in pro- and mature T cells) are identical to those in mice homozygous for Bcl2l11^tm1.1Ast alone

increased granulocyte number ( J:103605 )

• similar to mice homozygous for Bcl2l11^tm1.1Ast alone

decreased pre-B cell number ( J:103605 )

• in bone marrow

increased B cell number ( J:103605 )

• increase in mature B cells in the spleen and bone marrow similar to mice homozygous for Bcl2l11^tm1.1Ast alone

increased mature B cell number ( J:103605 )

• in bone marrow

increased T cell number ( J:103605 )

• increase in mature T cells in the spleen similar to mice homozygous for Bcl2l11^tm1.1Ast alone

increased monocyte cell number ( J:103605 )

• similar to mice homozygous for Bcl2l11^tm1.1Ast alone

abnormal lymphocyte physiology ( J:103605 )

• survival of mature T cells is increased following cytokine withdrawal or treatment with ionomycin similar to responses in mice homozygous for Bcl2l11^tm1.1Ast alone

cellular

azoospermia ( J:103605 )

♂

multinucleated giant male germ cells ( J:103605 )

♂

arrest of male meiosis ( J:103605 )

♂ • arrest is later than in Bax^tm1Sjk homozygotes as some round spermatids are present but no elongating spermatids are seen

hematopoietic system

enlarged spleen ( J:103605 )

• increase in size is similar to mice homozygous for Bcl2l11^tm1.1Ast alone

abnormal B cell differentiation ( J:103605 )

• in the bone marrow the pro/pre-B and immature B cell populations are reduced and the population of mature b cells is increased similar to mice homozygous for Bcl2l11^tm1.1Ast alone

decreased immature B cell number ( J:103605 )

• in bone marrow

decreased pro-B cell number ( J:103605 )

• in bone marrow

abnormal T cell differentiation ( J:103605 )

• abnormalities in T cell development in the thymus (decrease in pre-T cells and increase in pro- and mature T cells) are identical to those in mice homozygous for Bcl2l11^tm1.1Ast alone

increased granulocyte number ( J:103605 )

• similar to mice homozygous for Bcl2l11^tm1.1Ast alone

decreased pre-B cell number ( J:103605 )

• in bone marrow

increased B cell number ( J:103605 )

• increase in mature B cells in the spleen and bone marrow similar to mice homozygous for Bcl2l11^tm1.1Ast alone

increased mature B cell number ( J:103605 )

• in bone marrow

increased T cell number ( J:103605 )

• increase in mature T cells in the spleen similar to mice homozygous for Bcl2l11^tm1.1Ast alone

increased monocyte cell number ( J:103605 )

• similar to mice homozygous for Bcl2l11^tm1.1Ast alone

abnormal lymphocyte physiology ( J:103605 )

• survival of mature T cells is increased following cytokine withdrawal or treatment with ionomycin similar to responses in mice homozygous for Bcl2l11^tm1.1Ast alone

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:103605 )

♂ • variable abnormalities are seen including vacuolation, multi-nucleate syncytia, accumulation of spermatocytes, and apparent reduction in tubular cellularity, diameter, and lumen size

♂ • the spermatogonia layer is thicker than in wild-type being up to 3 cell layers thick

decreased testis weight ( J:103605 )

♂ • testes weight is reduced at P21 and in adults testes weigh about 60% that of wild-type; however serum concentrations of inhibin and follicle stimulating hormone are normal

Genotype
MGI:3800656

cx19

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Fas^lpr/Fas^lpr
• Genetic Background: B6.Cg-Bcl2l11^tm1.1Ast Fas^lpr

immune system

enlarged spleen ( J:132217 )

• severely enlarged by 16 weeks

spleen hyperplasia ( J:132217 )

increased dendritic cell number ( J:132217 )

• increased in spleen relative to Fas^lpr homozygotes

decreased B cell number ( J:132217 )

• lower in spleen and lymph node compared to wild-type or single mutants

abnormal T cell number ( J:132217 )

• mice show reduced amount of nae T cells compared to wild-type or Bcl2l11-deficient mice

• no difference in number of regulatory T cells is observed

abnormal T cell subpopulation ratio ( J:132217 )

• T cell subpopulations in the spleen and lymph nodes including single-positive, central memory and effector memory T cells are increased compared to single-deficient mice

increased memory T cell number ( J:132217 )

• increased memory T cell numbers in spleen and lymph nodes relative to single mutant animals

increased leukocyte cell number ( J:132217 )

• number of CD45+ cells is increased 4.6-fold vs wild-type, 3.2-fold vs Fas^lpr homozygotes, and 2.8-fold vs Bcl2l11-deficient mice

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased 30-fold relative to wild-type, 2-fold relative to Bcl2l11-deficient and 4-fold relative to Fas^lpr homozygous mice

increased transitional stage B cell number ( J:132217 )

• number of T1 and T2 B cells is increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased macrophage cell number ( J:132217 )

• increased numbers in spleen and lymph nodes are observed

abnormal effector T cell morphology ( J:132217 )

• increased effector memory T cell numbers in spleen and lymph nodes relative to single mutant animals

decreased spleen red pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by decreased red pulp amount

increased spleen white pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by increased white pulp amount

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is disturbed; ratio is higher significantly higher than wild-type, Bcl2l11-deficient mice or Fas^lpr homozygotes

• increased B cell number; CD19+ B cells are increased by 4.3-fold over wild-type, 1.8-fold over Bcl2l11-null mice and by 3.6-fold over Fas^lpr mice

abnormal lymph node cell ratio ( J:132217 )

• CD19+ B cells are increased 2.2-fold over wild-type and Bcl2l11-deficient mice

• no difference from B cell number in Fas^lpr mice

enlarged lymph nodes ( J:132217 )

• severely enlarged by 16 weeks

lymph node hyperplasia ( J:132217 )

increased susceptibility to autoimmune disorder ( J:132217 )

• on a normally resistant background, mice develop extreme lymphadenopathy and SLE

increased autoantibody level ( J:132217 )

• total anti-IgM and total anti-IgG antibody levels are increased compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice; anti-nuclear, anti-cytoplasmic and anti-glomerular antibodies are increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased anti-nuclear antigen antibody level ( J:132217 )

• anti-nuclear antibodies are increased compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased anti-double stranded DNA antibody level ( J:132217 )

• anti-dsDNA IgM and IgG antibodies are increased compared to wild-type and Bcl2l11-deficient mice; anti-dsDNA IgM antibody levels are increased over levels in Fas^lpr homozygotes

increased anti-histone antibody level ( J:132217 )

• increased compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased anti-single stranded DNA antibody level ( J:132217 )

• anti-ssDNA IgM and IgG antibodies are increased compared to wild-type and Bcl2l11-deficient mice; anti-ssDNA IgM antibody levels are increased over levels in Fas^lpr homozygotes

hematopoietic system

enlarged spleen ( J:132217 )

• severely enlarged by 16 weeks

spleen hyperplasia ( J:132217 )

increased dendritic cell number ( J:132217 )

• increased in spleen relative to Fas^lpr homozygotes

decreased B cell number ( J:132217 )

• lower in spleen and lymph node compared to wild-type or single mutants

abnormal T cell number ( J:132217 )

• mice show reduced amount of nae T cells compared to wild-type or Bcl2l11-deficient mice

• no difference in number of regulatory T cells is observed

abnormal T cell subpopulation ratio ( J:132217 )

• T cell subpopulations in the spleen and lymph nodes including single-positive, central memory and effector memory T cells are increased compared to single-deficient mice

increased memory T cell number ( J:132217 )

• increased memory T cell numbers in spleen and lymph nodes relative to single mutant animals

increased leukocyte cell number ( J:132217 )

• number of CD45+ cells is increased 4.6-fold vs wild-type, 3.2-fold vs Fas^lpr homozygotes, and 2.8-fold vs Bcl2l11-deficient mice

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased 30-fold relative to wild-type, 2-fold relative to Bcl2l11-deficient and 4-fold relative to Fas^lpr homozygous mice

increased transitional stage B cell number ( J:132217 )

• number of T1 and T2 B cells is increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased macrophage cell number ( J:132217 )

• increased numbers in spleen and lymph nodes are observed

abnormal effector T cell morphology ( J:132217 )

• increased effector memory T cell numbers in spleen and lymph nodes relative to single mutant animals

decreased spleen red pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by decreased red pulp amount

increased spleen white pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by increased white pulp amount

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is disturbed; ratio is higher significantly higher than wild-type, Bcl2l11-deficient mice or Fas^lpr homozygotes

• increased B cell number; CD19+ B cells are increased by 4.3-fold over wild-type, 1.8-fold over Bcl2l11-null mice and by 3.6-fold over Fas^lpr mice

renal/urinary system

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type and single mutant mice

increased kidney cell proliferation ( J:132217 )

• glomerular proliferation is increased

abnormal kidney morphology ( J:132217 )

• significant increase in renal B cells (CD19+) compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

• number of macrophages surrounding glomeruli is increased compared to wild-type and Fas^lpr homozygotes; macrophage index is 2.5-fold higher than in Fas homozygotes

abnormal renal glomerulus basement membrane morphology ( J:132217 )

• IgG deposits mainly localized to basement glomerular membrane are increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased renal glomerulus basement membrane thickness ( J:132217 )

• glomerular basement membrane thickening

abnormal renal glomerulus morphology ( J:132217 )

• mesangial expansion, basement membrane thickening, increased interstitial infiltration, and loss of open capillary loops are characteristic hallmarks of renal damage observed

• kidney damage pathological scores are increased over wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient glomeruli

• glomerular proliferation is increased

abnormal glomerular capillary morphology ( J:132217 )

• loss of open capillary loops

expanded mesangial matrix ( J:132217 )

• mesangial expansion

renal glomerulus hypertrophy ( J:132217 )

• glomerular size is increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

cellular

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type and single mutant mice

increased kidney cell proliferation ( J:132217 )

• glomerular proliferation is increased

cardiovascular system

abnormal glomerular capillary morphology ( J:132217 )

• loss of open capillary loops

growth/size/body

enlarged spleen ( J:132217 )

• severely enlarged by 16 weeks

spleen hyperplasia ( J:132217 )

Genotype
MGI:4366842

cx20

• Allelic Composition: Bcl2^tm1Dlo/Bcl2^tm1Dlo; Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast
• Genetic Background: B6.Cg-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast

hematopoietic system

increased spleen weight ( J:153846 )

• spleens are much heavier than those in homozygous Bcl-2 deficient mice

increased leukocyte cell number ( J:153846 )

• white blood cells numbers are much higher than in homozygous Bcl-2 deficient mice

immune system

increased spleen weight ( J:153846 )

• spleens are much heavier than those in homozygous Bcl-2 deficient mice

increased leukocyte cell number ( J:153846 )

• white blood cells numbers are much higher than in homozygous Bcl-2 deficient mice

growth/size/body

increased spleen weight ( J:153846 )

• spleens are much heavier than those in homozygous Bcl-2 deficient mice

Genotype
MGI:4366843

cx21

• Allelic Composition: Bcl2^tm1Dlo/Bcl2^tm1Dlo; Bcl2l11^tm1.1Ast/Bcl2l11⁺
• Genetic Background: B6.Cg-Bcl2^tm1Dlo Bcl2l11^tm1.1Ast

hematopoietic system

increased spleen weight ( J:153846 )

• spleens are heavier than those in homozygous Bcl-2 deficient mice

increased leukocyte cell number ( J:153846 )

• more white blood cells numbers than in homozygous Bcl-2 deficient mice

immune system

increased spleen weight ( J:153846 )

• spleens are heavier than those in homozygous Bcl-2 deficient mice

increased leukocyte cell number ( J:153846 )

• more white blood cells numbers than in homozygous Bcl-2 deficient mice

growth/size/body

increased spleen weight ( J:153846 )

• spleens are heavier than those in homozygous Bcl-2 deficient mice

Genotype
MGI:5521638

cx22

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Gata1^tm1.1Yen/Gata1^tm1.1Yen
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

hematopoietic system

decreased erythroid progenitor cell number ( J:200716 )

• colony forming erythroid cells in the bone marrow

Genotype
MGI:5300539

cx23

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Zbtb1^m1Btlr/Zbtb1^m1Btlr
• Genetic Background: involves: 129S1/Sv * C3H/HeN * C57BL/6 * C57BL/6J

hematopoietic system

absent T cells ( J:178820 )

• T cells fail to develop

immune system

absent T cells ( J:178820 )

• T cells fail to develop

Genotype
MGI:6267420

cx24

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Mlf1^tm1Swm/Mlf1^tm1Swm
• Genetic Background: involves: 129S1/Sv * C57BL/6

cellular

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type and Bcl2l11^tm1.1Ast homozygous cells

decreased splenocyte apoptosis ( J:266833 )

• almost no loss of cellular viability ex vivo upon cytokine depletion compared with wild-type and Bcl2l11^tm1.1Ast homozygous cells

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type and Bcl2l11^tm1.1Ast homozygous cells

hematopoietic system

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type and Bcl2l11^tm1.1Ast homozygous cells

decreased splenocyte apoptosis ( J:266833 )

• almost no loss of cellular viability ex vivo upon cytokine depletion compared with wild-type and Bcl2l11^tm1.1Ast homozygous cells

immune system

decreased thymocyte apoptosis ( J:266833 )

• ex vivo upon cytokine depletion compared with wild-type and Bcl2l11^tm1.1Ast homozygous cells

decreased splenocyte apoptosis ( J:266833 )

• almost no loss of cellular viability ex vivo upon cytokine depletion compared with wild-type and Bcl2l11^tm1.1Ast homozygous cells

Genotype
MGI:3720170

cx25

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Pmaip1^tm1Ast/Pmaip1^tm1Ast
• Genetic Background: involves: 129S1/Sv * C57BL/6

immune system

abnormal NK cell morphology ( J:123409 )

• following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells and Bcl2l11^tm1.1Ast homozygotes

hematopoietic system

abnormal NK cell morphology ( J:123409 )

• following expansion in culture, NK cells survive IL-15 withdrawal better than wild-type cells and Bcl2l11^tm1.1Ast homozygotes

Genotype
MGI:3803618

cx26

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Bnip3l^{Gt(XT0573)Wtsi}/Bnip3l^{Gt(XT0573)Wtsi}
• Genetic Background: involves: 129S1/Sv * C57BL/6

hematopoietic system

decreased erythrocyte cell number ( J:137609 )

decreased lymphocyte cell number ( J:137609 )

immune system

decreased lymphocyte cell number ( J:137609 )

Genotype
MGI:5529023

cx27

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Mirc14^tm1.2Flv/Mirc14^tm1.2Flv
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6N * FVB/N * SJL

immune system

decreased NK T cell number ( J:203157 )

• in the thymus, spleen and liver of mice treated with alpha- galactosylceramide CD1d1 tetramer

hematopoietic system

decreased NK T cell number ( J:203157 )

• in the thymus, spleen and liver of mice treated with alpha- galactosylceramide CD1d1 tetramer

Genotype
MGI:5562714

cx28

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Il15^tm1Imx/Il15^tm1Imx
• Genetic Background: involves: C57BL/6

immune system

immune system phenotype ( J:208318 )

N • middle-aged mice exhibit a rescue of regulatory T cells compared with Il15^tm1Imx homozygotes