Phenotypes Associated with This Genotype

Genotype
MGI:3847256

• Allelic Composition: Tnfrsf13b^tm1Vmd/Tnfrsf13b^tm1Vmd
• Genetic Background: involves: C57BL/6

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

mortality/aging

premature death ( J:82331 )

• 40% of mice die by 18 months of age

immune system

increased B cell proliferation ( J:70172 )

• B cells hyperproliferate in vitro in response to mitogenic or costimulatory stimuli

• B cells also hyperproliferate in response to Tnfsf13b ligand (BAFF, Blys)

increased B cell number ( J:70172 , J:82331 )

• total B cell numbers in the spleen and mesenteric lymph nodes is about double of controls (J:70172)

• B cell numbers are increased 2-3 fold in the spleen and lymph nodes (J:82331)

increased transitional stage B cell number ( J:70172 )

• the number of T1 B cells found in the spleen is about double of controls

increased mature B cell number ( J:70172 )

• number of mature B cells in the spleen is about double of controls

increased follicular B cell number ( J:70172 )

• number of follicular B cells in the spleen is 3 fold higher than controls

increased marginal zone B cell number ( J:70172 )

• number of marginal zone B cells in the spleen is 4-5 fold higher than controls

abnormal spleen morphology ( J:70172 )

enlarged spleen ( J:70172 , J:82331 )

• spleen of mice is enlarged (J:70172)

• spleen of mice is enlarged (J:82331)

abnormal spleen primary B follicle morphology ( J:70172 )

• B cell follicles are expanded in cellularity and size

increased spleen germinal center size ( J:70172 )

• germinal centers are expanded in these mice

abnormal spleen periarteriolar lymphoid sheath morphology ( J:70172 , J:82331 )

• the PALS region appears expanded in the spleen despite the presence of normal number of T cells (J:70172)

• PALS area is increased (J:82331)

increased spleen white pulp amount ( J:70172 )

• white pulp is expanded by increased numbers of follicle and marginal zone B cells

abnormal immunoglobulin level ( J:70172 )

• B cells produce higher levels of immunoglobulins in vitro in response to anti-CD40 stimulus

• mice have 70% higher levels of total and antigen-specific IgG1 in response to immunization with a thymus-dependent antigen

increased IgG1 level ( J:70172 )

• mice have 70% higher levels of total and antigen-specific IgG1 in response to immunization with a thymus-dependent antigen

abnormal Peyer's patch follicle morphology ( J:70172 )

• B cell follicles are inconsistently expanded in cellularity and size

abnormal lymph node primary follicle morphology ( J:70172 , J:82331 )

• B cell follicles are inconsistently expanded in cellularity and size (J:70172)

• follicle size is increased in these mice (J:82331)

enlarged lymph nodes ( J:70172 , J:82331 )

• axillary and mesenteric lymph nodes are enlarged (J:70172)

• lymph nodes are enlarged (J:82331)

increased anti-nuclear antigen antibody level ( J:82331 )

• titers of anti-nuclear antibodies are much higher than controls

increased anti-double stranded DNA antibody level ( J:82331 )

• titers of anti-dsDNA are much higher than controls

liver inflammation ( J:82331 )

• lymphocytic infiltrate is observed in the liver

kidney inflammation ( J:82331 )

• lymphocytic infiltrate is observed in the kidney

glomerulonephritis ( J:82331 )

• kidneys have mesangial proliferation and inflammatory cell infiltrates

• fibroid necrosis and sclerosis are visible in affected glomeruli with occasional crescent formation

• significant deposition of IgG is detectable in the glomeruli of 90% of mice

renal/urinary system

increased mesangial cell number ( J:82331 )

increased urine protein level ( J:82331 )

• levels of proteinuria gradually increase until by 7 months of age all mice have proteinurea greater than 100 mg/dl and 90% of proteinura greater than 300 mg/dl

kidney inflammation ( J:82331 )

• lymphocytic infiltrate is observed in the kidney

glomerulonephritis ( J:82331 )

• kidneys have mesangial proliferation and inflammatory cell infiltrates

• fibroid necrosis and sclerosis are visible in affected glomeruli with occasional crescent formation

• significant deposition of IgG is detectable in the glomeruli of 90% of mice

glomerulosclerosis ( J:82331 )

glomerular crescent ( J:82331 )

• occasional crescent formation

renal glomerular immunoglobulin deposits ( J:82331 )

• significant deposition of IgG is detectable in the glomeruli of 90% of mice

renal glomerulus fibrosis ( J:82331 )

homeostasis/metabolism

increased urine protein level ( J:82331 )

• levels of proteinuria gradually increase until by 7 months of age all mice have proteinurea greater than 100 mg/dl and 90% of proteinura greater than 300 mg/dl

liver/biliary system

liver inflammation ( J:82331 )

• lymphocytic infiltrate is observed in the liver

hematopoietic system

increased B cell proliferation ( J:70172 )

• B cells hyperproliferate in vitro in response to mitogenic or costimulatory stimuli

• B cells also hyperproliferate in response to Tnfsf13b ligand (BAFF, Blys)

increased B cell number ( J:70172 , J:82331 )

• total B cell numbers in the spleen and mesenteric lymph nodes is about double of controls (J:70172)

• B cell numbers are increased 2-3 fold in the spleen and lymph nodes (J:82331)

increased transitional stage B cell number ( J:70172 )

• the number of T1 B cells found in the spleen is about double of controls

increased mature B cell number ( J:70172 )

• number of mature B cells in the spleen is about double of controls

increased follicular B cell number ( J:70172 )

• number of follicular B cells in the spleen is 3 fold higher than controls

increased marginal zone B cell number ( J:70172 )

• number of marginal zone B cells in the spleen is 4-5 fold higher than controls

abnormal spleen morphology ( J:70172 )

enlarged spleen ( J:70172 , J:82331 )

• spleen of mice is enlarged (J:70172)

• spleen of mice is enlarged (J:82331)

abnormal spleen primary B follicle morphology ( J:70172 )

• B cell follicles are expanded in cellularity and size

increased spleen germinal center size ( J:70172 )

• germinal centers are expanded in these mice

abnormal spleen periarteriolar lymphoid sheath morphology ( J:70172 , J:82331 )

• the PALS region appears expanded in the spleen despite the presence of normal number of T cells (J:70172)

• PALS area is increased (J:82331)

increased spleen white pulp amount ( J:70172 )

• white pulp is expanded by increased numbers of follicle and marginal zone B cells

abnormal immunoglobulin level ( J:70172 )

• B cells produce higher levels of immunoglobulins in vitro in response to anti-CD40 stimulus

• mice have 70% higher levels of total and antigen-specific IgG1 in response to immunization with a thymus-dependent antigen

increased IgG1 level ( J:70172 )

• mice have 70% higher levels of total and antigen-specific IgG1 in response to immunization with a thymus-dependent antigen

neoplasm

increased leukemia incidence ( J:82331 )

• about 15 % of mice develop a B cell leukemia by 8 months of age

• leukemia infiltrates both spleen and liver

• cells have basophilic cytosol, indistinct cell borders, oval open faced nuclei, and express B220

growth/size/body

enlarged spleen ( J:70172 , J:82331 )

• spleen of mice is enlarged (J:70172)

• spleen of mice is enlarged (J:82331)

cellular

increased mesangial cell number ( J:82331 )

increased B cell proliferation ( J:70172 )

• B cells hyperproliferate in vitro in response to mitogenic or costimulatory stimuli

• B cells also hyperproliferate in response to Tnfsf13b ligand (BAFF, Blys)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:82331