Phenotypes Associated with This Genotype

Genotype
MGI:3800656

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

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

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 )