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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Tg(Tnfsf13b)1Fma
transgene insertion 1, Fabienne Mackay
MGI:2386944
Summary 16 genotypes


Genotype
MGI:3841106
cx1
Allelic
Composition		 Cd40tm1Kik/Cd40tm1Kik
Tg(Tnfsf13b)1Fma/?
Genetic
Background		 B6.Cg-Cd40tm1Kik Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (11 available); any Cd40 mutation (53 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal class switch recombination ( J:113556 )
• B cells exhibit reduced class switching in response to T cell-dependent antigens
increased marginal zone B cell number ( J:113556 )
• the number of splenic marginal zone B cells is increased by about 3-fold
absent spleen germinal center ( J:113556 )
• mice are defective in germinal center formation upon after immunization
abnormal B cell activation ( J:113556 )
• B cells have a vigorous response to T cell independent antigens producing much higher levels of antigen-specific IgG1, IgG2a, IgG2b, IgG3, and IgA class antibodies than controls
increased anti-double stranded DNA antibody level ( J:113556 )
• anti-dsDNA antibodies of the IgM class, IgA class, and all IgG subclasses are found in circulation
• titers of these auto-antibodies increase with age
glomerulonephritis ( J:113556 )
• kidneys of 10-month old mice have necrotic lesions

renal/urinary system
increased urine protein level ( J:113556 )
• all 8-month old mice have proteinuria in their urine at 100-300 mg/dl concentration
glomerulonephritis ( J:113556 )
• kidneys of 10-month old mice have necrotic lesions
renal glomerular immunoglobulin deposits ( J:113556 )
• immunohistology of kidneys with severe lesions reveal numerous glomerular deposits of IgG

homeostasis/metabolism
increased urine protein level ( J:113556 )
• all 8-month old mice have proteinuria in their urine at 100-300 mg/dl concentration

hematopoietic system
abnormal class switch recombination ( J:113556 )
• B cells exhibit reduced class switching in response to T cell-dependent antigens
increased marginal zone B cell number ( J:113556 )
• the number of splenic marginal zone B cells is increased by about 3-fold
absent spleen germinal center ( J:113556 )
• mice are defective in germinal center formation upon after immunization
abnormal B cell activation ( J:113556 )
• B cells have a vigorous response to T cell independent antigens producing much higher levels of antigen-specific IgG1, IgG2a, IgG2b, IgG3, and IgA class antibodies than controls




Genotype
MGI:3841107
cx2
Allelic
Composition		 Chuktm2Mka/Chuktm2Mka
Tg(Tnfsf13b)1Fma/?
Genetic
Background		 B6.Cg-Chuktm2Mka Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chuktm2Mka mutation (0 available); any Chuk mutation (51 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
increased transitional stage B cell number ( J:113556 )
• numbers of T2 B cells are slightly enlarged in the spleen
decreased marginal zone B cell number ( J:113556 )
• marginal zone B cell numbers are reduced compared to controls
absent spleen marginal zone ( J:113556 )
• marginal zones could not be localized in these mice
abnormal B cell activation ( J:113556 )
• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls
• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background
• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background
increased anti-double stranded DNA antibody level ( J:113556 )
• anti-dsDNA antibodies of the IgM class are found in circulation
• titers of these auto-antibodies increase slightly with age
• no significantly elevated anti-dsDNA antibodies are found within the other immunoglobulin classes which differs from transgenic mice not homozygote for the Chuktm2Mka allele

homeostasis/metabolism
increased urine protein level ( J:113556 )
• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

renal/urinary system
increased urine protein level ( J:113556 )
• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

hematopoietic system
increased transitional stage B cell number ( J:113556 )
• numbers of T2 B cells are slightly enlarged in the spleen
decreased marginal zone B cell number ( J:113556 )
• marginal zone B cell numbers are reduced compared to controls
absent spleen marginal zone ( J:113556 )
• marginal zones could not be localized in these mice
abnormal B cell activation ( J:113556 )
• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls
• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background
• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background




Genotype
MGI:3841112
cx3
Allelic
Composition		 Nfkb1tm1Bal/Nfkb1tm1Bal
Tg(Tnfsf13b)1Fma/?
Genetic
Background		 B6.Cg-Nfkb1tm1Bal Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nfkb1tm1Bal mutation (3 available); any Nfkb1 mutation (102 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal class switch recombination ( J:113556 )
• class switch recombination mediated by T cell independent antigens or by BAFF incubation is defective in these mice
increased transitional stage B cell number ( J:113556 )
• numbers of T1 B cells in the spleen are increased almost 3-fold while T2 numbers are almost about doubled
decreased marginal zone B cell number ( J:113556 )
• marginal zone B cells are almost completely absent in the spleen
abnormal B cell activation ( J:113556 )
• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM class antibodies than wild-type controls
• the Nfkb1 null background significantly reduced the IgG2a and IgG2b responses and virtually abrogated the IgG3 and IgA responses compared to transgenic mice on a wild-type background

immune system
immune system phenotype ( J:113556 )
N
• there are no elevated levels of anti-dsDNA antibodies detected in circulation compared to transgenic mice on a wild-type background that have high levels of auto-antbodies
abnormal class switch recombination ( J:113556 )
• class switch recombination mediated by T cell independent antigens or by BAFF incubation is defective in these mice
increased transitional stage B cell number ( J:113556 )
• numbers of T1 B cells in the spleen are increased almost 3-fold while T2 numbers are almost about doubled
decreased marginal zone B cell number ( J:113556 )
• marginal zone B cells are almost completely absent in the spleen
abnormal B cell activation ( J:113556 )
• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM class antibodies than wild-type controls
• the Nfkb1 null background significantly reduced the IgG2a and IgG2b responses and virtually abrogated the IgG3 and IgA responses compared to transgenic mice on a wild-type background




Genotype
MGI:3841109
cx4
Allelic
Composition		 Nfkb2tm2Brv/Nfkb2tm2Brv
Tg(Tnfsf13b)1Fma/?
Genetic
Background		 B6.Cg-Nfkb2tm2Brv Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nfkb2tm2Brv mutation (1 available); any Nfkb2 mutation (49 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
immune system phenotype ( J:113556 )
N
• there are no elevated levels of anti-dsDNA antibodies detected in circulation compared to transgenic mice on a wild-type background that have high levels of auto-antbodies
decreased marginal zone B cell number ( J:113556 )
• marginal zone B cells are almost completely absent in the spleen
absent spleen marginal zone ( J:113556 )
• marginal zones are absent in these mice
abnormal B cell activation ( J:113556 )
• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls
• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background
• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background

homeostasis/metabolism
increased urine protein level ( J:113556 )
• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

renal/urinary system
increased urine protein level ( J:113556 )
• about half of 8-month old mice have proteinuria in their urine at 30 mg/dl concentration

hematopoietic system
decreased marginal zone B cell number ( J:113556 )
• marginal zone B cells are almost completely absent in the spleen
absent spleen marginal zone ( J:113556 )
• marginal zones are absent in these mice
abnormal B cell activation ( J:113556 )
• B cells have a strong response to T cell independent antigens producing higher levels of antigen-specific IgM, IgG2a, IgG2b class antibodies than wild-type controls
• however, there is no significant elevation of antigen-specific IgG1, IgG3, and IgA antibodies as is observed in transgenic mice on a wild-type background
• levels of antibodies produced are also lower than those in transgenic mice on a wild-type background




Genotype
MGI:3841116
cx5
Allelic
Composition		 Tg(Tnfsf13b)1Fma/?
Tnfrsf13btm1Rjb/Tnfrsf13btm1Rjb
Genetic
Background		 B6.Cg-Tnfrsf13btm1Rjb Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Tnfsf13b)1Fma mutation (0 available)
Tnfrsf13btm1Rjb mutation (0 available); any Tnfrsf13b mutation (18 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal class switch recombination ( J:113556 )
• class switch recombination mediated by T cell independent antigens is defective in these mice

immune system
abnormal class switch recombination ( J:113556 )
• class switch recombination mediated by T cell independent antigens is defective in these mice




Genotype
MGI:3841115
cx6
Allelic
Composition		 Tg(Tnfsf13b)1Fma/?
Tnfrsf13ctm1Mass/Tnfrsf13ctm1Mass
Genetic
Background		 B6.Cg-Tnfrsf13ctm1Mass Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Tnfsf13b)1Fma mutation (0 available)
Tnfrsf13ctm1Mass mutation (1 available); any Tnfrsf13c mutation (15 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal class switch recombination ( J:113556 )
• class switch recombination mediated by BAFF incubation is defective in these mice

immune system
abnormal class switch recombination ( J:113556 )
• class switch recombination mediated by BAFF incubation is defective in these mice




Genotype
MGI:3692946
cx7
Allelic
Composition		 Tg(Tnfsf13b)1Fma/0
Tnfsf14tm1Kpf/Tnfsf14tm1Kpf
Genetic
Background		 involves: 129P2/OlaHsd * C57BL/6 * DBA/2J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Tnfsf13b)1Fma mutation (0 available)
Tnfsf14tm1Kpf mutation (2 available); any Tnfsf14 mutation (27 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
increased B cell number ( J:114782 )
• a marked increase in some B cell subsets compared to wild-type is detected in 12 week old mice
increased plasma cell number ( J:114782 )
• there is an increased frequency of B220neg/lo, IgA+ plasma cells in lamina propria preparations
abnormal spleen germinal center morphology ( J:114782 )
• numerous germinal centers are observed in B cell follicles of mutants
abnormal spleen marginal zone morphology ( J:114782 )
• splenic marginal zone is increased in size
increased IgA level ( J:114782 )
• augmented IgA staining is found in lamina propria of mutants

renal/urinary system
abnormal mesangial cell morphology ( J:114782 )
• in 8-month old mice, some thickening of mesangial and basement membranes
renal glomerular immunoglobulin deposits ( J:114782 )
• deposition of IgA in nearly all glomeruli is detected, similar to Tnfsf14-sufficient transgenic mice

immune system
increased B cell number ( J:114782 )
• a marked increase in some B cell subsets compared to wild-type is detected in 12 week old mice
increased plasma cell number ( J:114782 )
• there is an increased frequency of B220neg/lo, IgA+ plasma cells in lamina propria preparations
abnormal spleen germinal center morphology ( J:114782 )
• numerous germinal centers are observed in B cell follicles of mutants
abnormal spleen marginal zone morphology ( J:114782 )
• splenic marginal zone is increased in size
increased IgA level ( J:114782 )
• augmented IgA staining is found in lamina propria of mutants

cellular
abnormal mesangial cell morphology ( J:114782 )
• in 8-month old mice, some thickening of mesangial and basement membranes




Genotype
MGI:4840220
cx8
Allelic
Composition		 Ighatm1(Myc)Janz/Igha+
Tg(Tnfsf13b)1Fma/0
Genetic
Background		 involves: 129S1/Sv * C57BL/6 * DBA/2J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ighatm1(Myc)Janz mutation (1 available); any Igha mutation (18 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
premature death ( J:166158 )
• median lifespan of mice with leukemia is 10 months

hematopoietic system
enlarged spleen ( J:166158 )
• splenomegaly is obvious in males after 4 months of age
increased lymphocyte cell number ( J:166158 )
• males develop lymphocytosis at 3 months of age
increased B cell number ( J:166158 )
• males exhibit an increase in blood B-cell number, with an expansion of the CD5+CD3-B220low IgMlow B-cell population in blood and spleens
increased mature B cell number ( J:166158 )
• B-cell increase results from a monoclonal expansion of mature B cell-like cells
increased spleen white pulp amount ( J:166158 )
• 8 month old spleens of males exhibit enlarged white pulp with loss of normal splenic architecture resulting from a diffuse infiltration of mature lymphocytes

immune system
enlarged spleen ( J:166158 )
• splenomegaly is obvious in males after 4 months of age
increased lymphocyte cell number ( J:166158 )
• males develop lymphocytosis at 3 months of age
increased B cell number ( J:166158 )
• males exhibit an increase in blood B-cell number, with an expansion of the CD5+CD3-B220low IgMlow B-cell population in blood and spleens
increased mature B cell number ( J:166158 )
• B-cell increase results from a monoclonal expansion of mature B cell-like cells
increased spleen white pulp amount ( J:166158 )
• 8 month old spleens of males exhibit enlarged white pulp with loss of normal splenic architecture resulting from a diffuse infiltration of mature lymphocytes

neoplasm
increased chronic lymphocytic leukemia incidence ( J:166158 )
• mutants, mainly males, develop a CD5+ B-cell lymphoproliferative disease by 8 months of age that resembles human chronic lymphocytic leukemia
• male mice exhibit increased splenic 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) uptake suggesting elevated leukemic cell metabolism

growth/size/body
enlarged spleen ( J:166158 )
• splenomegaly is obvious in males after 4 months of age




Genotype
MGI:5300899
cx9
Allelic
Composition		 Ighatm1Grh/Ighatm1Grh
Tg(Tnfsf13b)1Fma/Tg(Tnfsf13b)1Fma
Genetic
Background		 involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ighatm1Grh mutation (2 available); any Igha mutation (18 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
immune system phenotype ( J:178227 )
N
• double mutant do not exhibit the impaired kidney function seen in single Tg(Tnfsf13b)1Fma homozygotes and have reduced levels of serum IgA and IgA deposits in the kidney, and reduced hematuria, urinary protein and albumin levels indicating that IgA is important for renal disease development in Tg(Tnfsf13b)1Fma homozygotes




Genotype
MGI:3789188
cx10
Allelic
Composition		 Nba10NZB/Nba10NZB
Tg(Tnfsf13b)1Fma/0
Genetic
Background		 involves: C57BL/6 * DBA/2J * NZB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nba10NZB mutation (1 available); any Nba10 mutation (1 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
increased B cell number ( J:134128 )
• increased total splenic B cell numbers
increased IgG level ( J:134128 )
• increased total serum IgG antibodies
increased IgM level ( J:134128 )
• increased total serum IgM antibodies
increased susceptibility to systemic lupus erythematosus ( J:134128 )
• increased serum IgG and IgM antibodies
• increased incidence of glomerulonephritis by 3 months of age
increased anti-double stranded DNA antibody level ( J:134128 )
• increased serum IgG anti-dsDNA Abs shows positive correlation to glomerulonephritis severity
glomerulonephritis ( J:134128 )
• increased glomerulonephritis incidence at 3 months of age

renal/urinary system
glomerulonephritis ( J:134128 )
• increased glomerulonephritis incidence at 3 months of age

hematopoietic system
increased B cell number ( J:134128 )
• increased total splenic B cell numbers
increased IgG level ( J:134128 )
• increased total serum IgG antibodies
increased IgM level ( J:134128 )
• increased total serum IgM antibodies




Genotype
MGI:3789187
cx11
Allelic
Composition		 Sle1NZW/Sle1NZW
Tg(Tnfsf13b)1Fma/0
Genetic
Background		 involves: C57BL/6 * DBA/2J * NZW
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sle1NZW mutation (0 available); any Sle1 mutation (2 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
increased B cell number ( J:134128 )
• increased total splenic B cell numbers
increased IgG level ( J:134128 )
• increased total serum IgG antibodies
increased IgM level ( J:134128 )
• increased total serum IgM antibodies
increased susceptibility to systemic lupus erythematosus ( J:134128 )
• increased serum IgG and IgM antibodies
• increased incidence of glomerulonephritis by 3 months of age
glomerulonephritis ( J:134128 )
• increased glomerulonephritis incidence at 3 months of age

renal/urinary system
glomerulonephritis ( J:134128 )
• increased glomerulonephritis incidence at 3 months of age

hematopoietic system
increased B cell number ( J:134128 )
• increased total splenic B cell numbers
increased IgG level ( J:134128 )
• increased total serum IgG antibodies
increased IgM level ( J:134128 )
• increased total serum IgM antibodies




Genotype
MGI:5300824
tg12
Allelic
Composition		 Tg(Tnfsf13b)1Fma/Tg(Tnfsf13b)1Fma
Genetic
Background		 involves: C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging

immune system
increased B cell number ( J:178227 )
• mutants exhibit an increased percentage of B cells in mucosal lymphoid tissues, including the gut lamina propria and the mesenteric lymph nodes, and in the spleen
• both specific pathogen free and germ-free mutants exhibit B cell hyperplasia in the spleen
increased transitional stage T2 B cell number ( J:178227 )
• both specific pathogen free and germ-free mutants exhibit expanded percentages of transitional 2 B cells
increased marginal zone B cell number ( J:178227 )
• both specific pathogen free and germ-free mutants exhibit expanded percentages of splenic marginal zone B cells
abnormal immunoglobulin level ( J:178227 )
• serum IgA level in germ-free mutants is decreased about 100-fold compared to specific-pathogen free mutants but is similar to those for germ-free wild-type mutants
• germ-free mutants do not exhibit increased IgA in plasma cells in the gut and deposition of IgA in the glomeruli as is seen in conventionally housed specific pathogen free mutants
increased immunoglobulin level ( J:178227 )
• while IgM and IgA levels are elevated in mutants, serum IgG levels and antinuclear IgG antibodies are not elevated in mutants
increased IgA level ( J:178227 )
• by 8 months of age, most mutants exhibit IgA mesangial deposition in the glomeruli, however little C4 deposition is seen
• IgA serum levels are elevated by 8 weeks of age in males and remain at this elevated level until 6 to 8 months of age, at which point, IgA levels begin to drop
• in most females, serum IgA levels do not rise
• serum IgA in mutants is aberrantly glycosylated, with reduced amounts of terminal galactose and sialic acid, is polymeric and is not associated with the secretory component
• germ-free mutants colonized with a limited commensal microbiota called altered Schaedler flora (ASF) at 6 weeks of age exhibit an increase in serum IgA levels that continue to increase until about 3.5 weeks and then stabilize compared to wild-type mice colonized with ASF
• conventionally housed specific pathogen free mutants colonized with ASF exhibit widespread dissemination of IgA+ plasma cells in the periphery while germ-free mutants housed in a barrier facility do not show IgA+ plasma cells in the periphery after colonization, indicating that the hyper-IgA syndrome is influenced by ongoing-commensual-dependent signaling in the intestine
increased IgM level ( J:178227 )
• mutants with mild proteinuria at 6-8 months of age, exhibit mesangial deposits of IgM in the glomeruli
• IgM serum levels are elevated by 8 weeks of age
kidney inflammation ( J:178227 )
• mutants develop severe and fatal nephritis by 17 months of age
• males develop nephritis faster than females and this gender bias is thought to result from sexual dimorphism in expression in the kidneys of the alpha1-antitrypsin driven transgene

homeostasis/metabolism
albuminuria ( J:178227 )
• by 6 months of age, mutants exhibit modest albuminuria that gets worse with age

hematopoietic system
increased B cell number ( J:178227 )
• mutants exhibit an increased percentage of B cells in mucosal lymphoid tissues, including the gut lamina propria and the mesenteric lymph nodes, and in the spleen
• both specific pathogen free and germ-free mutants exhibit B cell hyperplasia in the spleen
increased transitional stage T2 B cell number ( J:178227 )
• both specific pathogen free and germ-free mutants exhibit expanded percentages of transitional 2 B cells
increased marginal zone B cell number ( J:178227 )
• both specific pathogen free and germ-free mutants exhibit expanded percentages of splenic marginal zone B cells
abnormal immunoglobulin level ( J:178227 )
• serum IgA level in germ-free mutants is decreased about 100-fold compared to specific-pathogen free mutants but is similar to those for germ-free wild-type mutants
• germ-free mutants do not exhibit increased IgA in plasma cells in the gut and deposition of IgA in the glomeruli as is seen in conventionally housed specific pathogen free mutants
increased immunoglobulin level ( J:178227 )
• while IgM and IgA levels are elevated in mutants, serum IgG levels and antinuclear IgG antibodies are not elevated in mutants
increased IgA level ( J:178227 )
• by 8 months of age, most mutants exhibit IgA mesangial deposition in the glomeruli, however little C4 deposition is seen
• IgA serum levels are elevated by 8 weeks of age in males and remain at this elevated level until 6 to 8 months of age, at which point, IgA levels begin to drop
• in most females, serum IgA levels do not rise
• serum IgA in mutants is aberrantly glycosylated, with reduced amounts of terminal galactose and sialic acid, is polymeric and is not associated with the secretory component
• germ-free mutants colonized with a limited commensal microbiota called altered Schaedler flora (ASF) at 6 weeks of age exhibit an increase in serum IgA levels that continue to increase until about 3.5 weeks and then stabilize compared to wild-type mice colonized with ASF
• conventionally housed specific pathogen free mutants colonized with ASF exhibit widespread dissemination of IgA+ plasma cells in the periphery while germ-free mutants housed in a barrier facility do not show IgA+ plasma cells in the periphery after colonization, indicating that the hyper-IgA syndrome is influenced by ongoing-commensual-dependent signaling in the intestine
increased IgM level ( J:178227 )
• mutants with mild proteinuria at 6-8 months of age, exhibit mesangial deposits of IgM in the glomeruli
• IgM serum levels are elevated by 8 weeks of age

renal/urinary system
albuminuria ( J:178227 )
• by 6 months of age, mutants exhibit modest albuminuria that gets worse with age
abnormal renal glomerulus morphology ( J:178227 )
• kidneys show expanded glomeruli and glomerular capillary thickening but no sclerosis
• with age, mutants display severe, global, and diffuse deposition of hyaline material in the glomeruli
abnormal mesangial cell morphology ( J:178227 )
• kidneys show rare mild mesangial cell proliferation but no glomerular sclerosis, tubular atrophy, or interstitial perivascular infiltration
expanded mesangial matrix ( J:178227 )
• kidneys exhibit segmental multifocal expansion of the mesangial matrix with hyaline materials
renal glomerulus atrophy ( J:178227 )
• mild focal tubular atrophy
abnormal kidney physiology ( J:178227 )
• mutants exhibit impaired kidney function by 14-15 months of age that is preceded by an elevation in IgA at 8-10 months of age
kidney inflammation ( J:178227 )
• mutants develop severe and fatal nephritis by 17 months of age
• males develop nephritis faster than females and this gender bias is thought to result from sexual dimorphism in expression in the kidneys of the alpha1-antitrypsin driven transgene

cellular
abnormal mesangial cell morphology ( J:178227 )
• kidneys show rare mild mesangial cell proliferation but no glomerular sclerosis, tubular atrophy, or interstitial perivascular infiltration

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
IgA glomerulonephritis DOID:2986 OMIM:161950
 J:178227




Genotype
MGI:3692945
tg13
Allelic
Composition		 Tg(Tnfsf13b)1Fma/0
Genetic
Background		 B6.Cg-Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal B cell differentiation ( J:73711 )
• IgM dull subset of B cells is larger in transgenic mice compared to control
• B220hi/IgMhi B cell subset is greatly increased in transgenic mice
• large IgMhi B cell subset is phenotypically different from the small IgMhi B cell subset in controls, resembling marginal zone B cells
increased B cell number ( J:114782 )
• a marked increase in some B cell subsets compared to wild-type is detected in 12 week old mice
increased B-1a cell number ( J:114782 )
• presence of B-1a (CD5+) B cells are detected compared to controls
increased B-1b cell number ( J:114782 )
• a 3-fold increase in B-1b (CD5-) B cells
increased plasma cell number ( J:114782 )
• there is an increased frequency of B220neg/lo, IgA+ plasma cells in lamina propria preparations (mutants 45.5% vs wild-type 14.4%)
abnormal spleen germinal center morphology ( J:114782 )
• numerous germinal centers are observed in B cell follicles of young transgenic mice compared to wild-type and aged transgenic mice
abnormal spleen marginal zone morphology ( J:114782 )
• splenic marginal zone is increased in size, particularly notable in aged mice
increased IgA level ( J:114782 )
• mice exhibit elevated levels in both steady state and in response to antigen stimulation; at 12 weeks of age, IgA levels are increased 1500-fold over wild-type (22.7 mg/ml IgA vs 0.015 mg/ml in wild-type - hyper-IgA)
• augmented IgA staining is found in lamina propria of transgenic mice

immune system
salivary gland inflammation ( J:73711 )
• 60% of mice over 12 months of age have severely inflamed salivary glands with large leukocytic infiltrates
abnormal B cell differentiation ( J:73711 )
• IgM dull subset of B cells is larger in transgenic mice compared to control
• B220hi/IgMhi B cell subset is greatly increased in transgenic mice
• large IgMhi B cell subset is phenotypically different from the small IgMhi B cell subset in controls, resembling marginal zone B cells
increased B cell number ( J:114782 )
• a marked increase in some B cell subsets compared to wild-type is detected in 12 week old mice
increased plasma cell number ( J:114782 )
• there is an increased frequency of B220neg/lo, IgA+ plasma cells in lamina propria preparations (mutants 45.5% vs wild-type 14.4%)
increased B-1a cell number ( J:114782 )
• presence of B-1a (CD5+) B cells are detected compared to controls
increased B-1b cell number ( J:114782 )
• a 3-fold increase in B-1b (CD5-) B cells
abnormal spleen germinal center morphology ( J:114782 )
• numerous germinal centers are observed in B cell follicles of young transgenic mice compared to wild-type and aged transgenic mice
abnormal spleen marginal zone morphology ( J:114782 )
• splenic marginal zone is increased in size, particularly notable in aged mice
increased IgA level ( J:114782 )
• mice exhibit elevated levels in both steady state and in response to antigen stimulation; at 12 weeks of age, IgA levels are increased 1500-fold over wild-type (22.7 mg/ml IgA vs 0.015 mg/ml in wild-type - hyper-IgA)
• augmented IgA staining is found in lamina propria of transgenic mice
kidney inflammation ( J:73711 )
• most mice over 13 months of age show signs of severe nephritis

renal/urinary system
increased urine protein level ( J:114782 )
• proteinuria is detected only in a subset of 8-month old mice
kidney inflammation ( J:73711 )
• most mice over 13 months of age show signs of severe nephritis
abnormal kidney morphology ( J:114782 )
• IgA immune complexes are detected in majority of young and aged mice
abnormal glomerular mesangium morphology ( J:114782 )
• significant IgA deposits are found specifically in kidney glomerular mesangium
renal glomerular immunoglobulin deposits ( J:114782 )
• IgA deposits are found in nearly all glomeruli, while deposits of each IgG, and IgM are also detected, while very little Ig deposition is found in wild-type kidneys
renal glomerulus hypertrophy ( J:114782 )
• in 8-month old mice, glomeruli are slightly enlarged and hypercellular

homeostasis/metabolism
decreased salivation ( J:73711 )
• mice aged 12-15.5 months of age produce significantly less saliva compared to age-matched controls; this difference is not observed in mice aged 8-10 months
increased urine protein level ( J:114782 )
• proteinuria is detected only in a subset of 8-month old mice

digestive/alimentary system
increased submandibular gland tumor incidence ( J:73711 )
• some mice (3 cases) have large submaxillary tumors which contain hyperplastic lymphoid tissue composed of activated B cells and numerous germinal centers; these abnormal aggregates of B lymphoid cells are found in lymphocytic infiltrates of some tumor-free mice
enlarged salivary gland ( J:73711 )
• many mice over 13 months of age have enlarged salivary glands
decreased salivation ( J:73711 )
• mice aged 12-15.5 months of age produce significantly less saliva compared to age-matched controls; this difference is not observed in mice aged 8-10 months
salivary gland inflammation ( J:73711 )
• 60% of mice over 12 months of age have severely inflamed salivary glands with large leukocytic infiltrates

endocrine/exocrine glands
increased submandibular gland tumor incidence ( J:73711 )
• some mice (3 cases) have large submaxillary tumors which contain hyperplastic lymphoid tissue composed of activated B cells and numerous germinal centers; these abnormal aggregates of B lymphoid cells are found in lymphocytic infiltrates of some tumor-free mice
enlarged salivary gland ( J:73711 )
• many mice over 13 months of age have enlarged salivary glands
decreased salivation ( J:73711 )
• mice aged 12-15.5 months of age produce significantly less saliva compared to age-matched controls; this difference is not observed in mice aged 8-10 months
salivary gland inflammation ( J:73711 )
• 60% of mice over 12 months of age have severely inflamed salivary glands with large leukocytic infiltrates

neoplasm
increased submandibular gland tumor incidence ( J:73711 )
• some mice (3 cases) have large submaxillary tumors which contain hyperplastic lymphoid tissue composed of activated B cells and numerous germinal centers; these abnormal aggregates of B lymphoid cells are found in lymphocytic infiltrates of some tumor-free mice

growth/size/body
increased submandibular gland tumor incidence ( J:73711 )
• some mice (3 cases) have large submaxillary tumors which contain hyperplastic lymphoid tissue composed of activated B cells and numerous germinal centers; these abnormal aggregates of B lymphoid cells are found in lymphocytic infiltrates of some tumor-free mice

craniofacial
increased submandibular gland tumor incidence ( J:73711 )
• some mice (3 cases) have large submaxillary tumors which contain hyperplastic lymphoid tissue composed of activated B cells and numerous germinal centers; these abnormal aggregates of B lymphoid cells are found in lymphocytic infiltrates of some tumor-free mice

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
Sjogren's syndrome DOID:12894 OMIM:270150
 J:73711




Genotype
MGI:3692929
tg14
Allelic
Composition		 Tg(Tnfsf13b)1Fma/0
Genetic
Background		 involves: C57BL/6 * DBA/2J
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
hematopoietic system phenotype ( J:58798 )
N
• total numbers of T and B cells in bone marrow of transgenic mice is similar to control
abnormal T cell number ( J:58798 )
• alterations in T cell numbers are present in transgenic mice
abnormal T cell subpopulation ratio ( J:58798 )
• absolute numbers of CD4 circulating T cells are reduced 50% compared to control; similar observations are made for CD8 T cell subset
increased T cell number ( J:58798 )
• total number of T cells in spleen and MLN of transgenics is increased 2-fold
increased lymphocyte cell number ( J:58798 )
• transgenic mice have higher numbers of circulating lymphocytes than nontransgenic littermates, with numbers as high as 13000 lymphocytes/ul blood
increased B cell number ( J:58798 )
• numbers of peripheral blood B cells are increased compared to controls; expansion of B cell compartment is observed, with global B cell activation
• total B cell number is 7-fold higher than in controls in spleen and mesenteric lymph nodes (MLN)
increased mature B cell number ( J:58798 )
• mature B cell number in spleen and mesenteric lymph nodes (MLN) is increased compared to controls
increased marginal zone B cell number ( J:58798 )
• proportion of marginal zone B cells is increased compared to controls, while fraction of newly formed B cells is slightly decreased
increased plasma cell number ( J:58798 )
• large numbers of plasma cells are present in spleen and mesenteric lymph nodes
abnormal B cell morphology ( J:58798 )
• B cell/T cell ratios are increased in transgenics
enlarged spleen ( J:58798 )
• mice have enlarged spleens compared to control
increased spleen B cell follicle size ( J:58798 )
• enlarged B cell follicles
abnormal spleen follicular dendritic cell network ( J:58798 )
• dendritic cells in T cell zone and marginal zone are reduced, compared to controls
increased spleen germinal center size ( J:58798 )
• spleens contain large and numerous germinal centers in absence of immunization compared to control
abnormal spleen periarteriolar lymphoid sheath morphology ( J:58798 )
• reduced periarteriolar lymphocyte sheath (or T cell area)
abnormal B cell physiology ( J:58798 )
• all B cells in peripheral blood have increased MHC II and Bcl2 expression compared to controls, indicating some level of activation
increased immunoglobulin level ( J:58798 )
• mice have hyperglobulinemia
increased IgG level ( J:58798 )
• IgG levels are elevated (50 mg/ml vs ~5-8 mg/ml in controls)
increased IgM level ( J:58798 )
• IgM levels are increased, but not as much as IgG levels
abnormal T cell physiology ( J:58798 )
• 40-56% of CD4 or CD8 T cells are activated, with a CD44hi, L-selectinlo phenotype, compared to only 8-12% in control littermates

immune system
abnormal T cell number ( J:58798 )
• alterations in T cell numbers are present in transgenic mice
abnormal T cell subpopulation ratio ( J:58798 )
• absolute numbers of CD4 circulating T cells are reduced 50% compared to control; similar observations are made for CD8 T cell subset
increased T cell number ( J:58798 )
• total number of T cells in spleen and MLN of transgenics is increased 2-fold
increased lymphocyte cell number ( J:58798 )
• transgenic mice have higher numbers of circulating lymphocytes than nontransgenic littermates, with numbers as high as 13000 lymphocytes/ul blood
increased B cell number ( J:58798 )
• numbers of peripheral blood B cells are increased compared to controls; expansion of B cell compartment is observed, with global B cell activation
• total B cell number is 7-fold higher than in controls in spleen and mesenteric lymph nodes (MLN)
increased mature B cell number ( J:58798 )
• mature B cell number in spleen and mesenteric lymph nodes (MLN) is increased compared to controls
increased marginal zone B cell number ( J:58798 )
• proportion of marginal zone B cells is increased compared to controls, while fraction of newly formed B cells is slightly decreased
increased plasma cell number ( J:58798 )
• large numbers of plasma cells are present in spleen and mesenteric lymph nodes
abnormal B cell morphology ( J:58798 )
• B cell/T cell ratios are increased in transgenics
enlarged spleen ( J:58798 )
• mice have enlarged spleens compared to control
increased spleen B cell follicle size ( J:58798 )
• enlarged B cell follicles
abnormal spleen follicular dendritic cell network ( J:58798 )
• dendritic cells in T cell zone and marginal zone are reduced, compared to controls
increased spleen germinal center size ( J:58798 )
• spleens contain large and numerous germinal centers in absence of immunization compared to control
abnormal spleen periarteriolar lymphoid sheath morphology ( J:58798 )
• reduced periarteriolar lymphocyte sheath (or T cell area)
abnormal B cell physiology ( J:58798 )
• all B cells in peripheral blood have increased MHC II and Bcl2 expression compared to controls, indicating some level of activation
increased immunoglobulin level ( J:58798 )
• mice have hyperglobulinemia
increased IgG level ( J:58798 )
• IgG levels are elevated (50 mg/ml vs ~5-8 mg/ml in controls)
increased IgM level ( J:58798 )
• IgM levels are increased, but not as much as IgG levels
abnormal T cell physiology ( J:58798 )
• 40-56% of CD4 or CD8 T cells are activated, with a CD44hi, L-selectinlo phenotype, compared to only 8-12% in control littermates
enlarged Peyer's patches ( J:58798 )
• Peyer's patches are enlarged
increased autoantibody level ( J:58798 )
• mice have increased levels of anti-IgG autoantibodies compared to controls; levels of rheumatoid factors (RF) and circulating immune complexes (CIC) are elevated

homeostasis/metabolism
increased urine protein level ( J:58798 )
• all transgenics display proteinuria

renal/urinary system
increased urine protein level ( J:58798 )
• all transgenics display proteinuria
abnormal kidney morphology ( J:58798 )
• immunoglobulin deposition in kidneys is detected

growth/size/body
enlarged spleen ( J:58798 )
• mice have enlarged spleens compared to control




Genotype
MGI:3692974
tg15
Allelic
Composition		 Tg(Tnfsf13b)1Fma/0
Genetic
Background		 involves: C57BL/6J * DBA/2J
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal B-1 B cell morphology ( J:115788 )
• expression of CD21/CD35 on B-1 cells from mutants is increased compared to wild-type

immune system
abnormal B-1 B cell morphology ( J:115788 )
• expression of CD21/CD35 on B-1 cells from mutants is increased compared to wild-type




Genotype
MGI:3841104
tg16
Allelic
Composition		 Tg(Tnfsf13b)1Fma/?
Genetic
Background		 B6.Cg-Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
increased B cell number ( J:113556 )
• splenic B cell numbers are about twice that of controls
increased transitional stage B cell number ( J:113556 )
• numbers of T1 B cells in the spleen are increased almost 3-fold while T2 numbers are almost about doubled
abnormal spleen marginal zone morphology ( J:113556 )
• the size of the marginal zone is increased
increased marginal zone B cell number ( J:113556 )
• the number of splenic marginal zone B cells is increased by about 3-fold
abnormal B cell activation ( J:113556 )
• B cells have a vigorous response to T cell independent antigens producing much higher levels of IgG1, IgG2a, IgG2b, IgG3, and IgA class immunoglobulins than controls
abnormal marginal zone B cell physiology ( J:113556 )
• marginal zone B cells (MZB) mediate autoimmune disease in these transgenic mice as demonstrated by auto-antibody production when MZB are transferred into transgenic mice on a B-cell deficient background
• MZB from transgenic mice have higher integrin adhesion activity
increased anti-double stranded DNA antibody level ( J:113556 )
• anti-dsDNA antibodies of the IgM class, IgA class, and all IgG subclasses are found in circulation
• titers of these auto-antibodies increase with
• splenectomy at three weeks of age significantly reduces IgG auto-antibodies and partially reduces auto-antibodies in the other subclasses
glomerulonephritis ( J:113556 )
• kidneys of 10-month old mice have necrotic lesions

renal/urinary system
increased urine protein level ( J:113556 )
• all 8-month old mice have proteinuria in their urine with most having 100-300 mg/dl
glomerulonephritis ( J:113556 )
• kidneys of 10-month old mice have necrotic lesions
renal glomerular immunoglobulin deposits ( J:113556 )
• immunohistology of kidneys with severe lesions reveal numerous glomerular deposits of IgG

homeostasis/metabolism
increased urine protein level ( J:113556 )
• all 8-month old mice have proteinuria in their urine with most having 100-300 mg/dl

hematopoietic system
increased B cell number ( J:113556 )
• splenic B cell numbers are about twice that of controls
increased transitional stage B cell number ( J:113556 )
• numbers of T1 B cells in the spleen are increased almost 3-fold while T2 numbers are almost about doubled
abnormal spleen marginal zone morphology ( J:113556 )
• the size of the marginal zone is increased
increased marginal zone B cell number ( J:113556 )
• the number of splenic marginal zone B cells is increased by about 3-fold
abnormal B cell activation ( J:113556 )
• B cells have a vigorous response to T cell independent antigens producing much higher levels of IgG1, IgG2a, IgG2b, IgG3, and IgA class immunoglobulins than controls
abnormal marginal zone B cell physiology ( J:113556 )
• marginal zone B cells (MZB) mediate autoimmune disease in these transgenic mice as demonstrated by auto-antibody production when MZB are transferred into transgenic mice on a B-cell deficient background
• MZB from transgenic mice have higher integrin adhesion activity




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11/05/2024
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