Phenotypes Associated with This Genotype

Genotype
MGI:2176744

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

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

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