Phenotypes associated with this allele

• Allele Symbol: Traf3ip2^tm1.1Lix
• Allele Name: targeted mutation 1.1, Xiaoxia Li
• Allele ID: MGI:3510784
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix	B6.129-Traf3ip2^tm1.1Lix	MGI:5440213
hm2	Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix	C.129-Traf3ip2^tm1.1Lix	MGI:5439184
hm3	Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix	involves: 129/Sv * BALB/c	MGI:3511165
cn4	Traf3ip2^tm1Lix/Traf3ip2^tm1.1Lix Tg(CD19-cre/ERT2)1Cgn/0	involves: 129/Sv * BALB/c	MGI:3511174
cx5	Tcrb^tm1Mom/Tcrb^tm1Mom Tcrd^tm1Mom/Tcrd^tm1Mom Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix	B6.129-Tcrb^tm1Mom Traf3ip2^tm1.1Lix Tcrd^tm1Mom	MGI:5440219
cx6	Cd40^tm1Kik/Cd40^tm1Kik Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix	involves: 129 * 129P2/OlaHsd * BALB/c	MGI:3511170
cx7	Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix Tnfsf13b^tm1Msc/Tnfsf13b^tm1Msc	involves: 129 * 129S2/SvPas * BALB/c	MGI:3511169

Genotype
MGI:5440213

hm1

• Allelic Composition: Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix
• Genetic Background: B6.129-Traf3ip2^tm1.1Lix

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

immune system

immune system phenotype ( J:187766 )

N • Background Sensitivity: while mutants on the C57BL/6 background develop lupus-like disease, they fail to develop Sjogrens syndrome-like disease as seen in the BALB/c background, showing no signs of enlarged submaxillary glands or elevated serum anti-SSB/La IgG autoantibodies

enlarged spleen ( J:187766 )

• in 32-40 week old mutants

increased spleen weight ( J:187766 )

• in 32-40 week old mutants

spleen hyperplasia ( J:187766 )

• in 32-40 week old mutants

abnormal transitional stage B cell morphology ( J:187766 )

• mutants exhibit a skewing in the repertoire from T1 to T2/T3 B cells resulting in ratios of T2:T1 and T3:T1 B cells that are increased compared to wild-type mice

increased B cell number ( J:187766 )

• number of B cells in the spleen shows a trend toward a statistical increase compared to controls

• however, number of T cells in the spleen is similar to wild-type

increased immature B cell number ( J:187766 )

• 16-18 week old mutants exhibit significantly increased numbers of total immature AA4.1+B220+ B cells

increased marginal zone B cell number ( J:187766 )

• mutants exhibit elevated levels of marginal zone B cells

• however, no increase in the number of follicular mature B cells is seen

increased IgG level ( J:187766 )

• 28-32 week old mutants exhibit hypergammaglobulinemia

• however levels of IgM are normal

increased IgG1 level ( J:187766 )

increased IgG2c level ( J:187766 )

lymph node hyperplasia ( J:187766 )

• increase in cervical lymph node weight and cellularity in 32-40 week old mutants

enlarged cervical lymph nodes ( J:187766 )

• increase in cervical lymph node weight and cellularity in 32-40 week old mutants

increased autoantibody level ( J:187766 )

increased anti-nuclear antigen antibody level ( J:187766 )

• 28-32 week old mutants exhibit elevated levels of serum anti-nuclear autoantibodies (anti-chromatin IgG, anti-histone IgG, and anti-dsDNA IgG)

increased anti-chromatin antibody level ( J:187766 )

increased anti-double stranded DNA antibody level ( J:187766 )

increased anti-histone antibody level ( J:187766 )

hematopoietic system

enlarged spleen ( J:187766 )

• in 32-40 week old mutants

increased spleen weight ( J:187766 )

• in 32-40 week old mutants

spleen hyperplasia ( J:187766 )

• in 32-40 week old mutants

abnormal transitional stage B cell morphology ( J:187766 )

• mutants exhibit a skewing in the repertoire from T1 to T2/T3 B cells resulting in ratios of T2:T1 and T3:T1 B cells that are increased compared to wild-type mice

increased B cell number ( J:187766 )

• number of B cells in the spleen shows a trend toward a statistical increase compared to controls

• however, number of T cells in the spleen is similar to wild-type

increased immature B cell number ( J:187766 )

• 16-18 week old mutants exhibit significantly increased numbers of total immature AA4.1+B220+ B cells

increased marginal zone B cell number ( J:187766 )

• mutants exhibit elevated levels of marginal zone B cells

• however, no increase in the number of follicular mature B cells is seen

increased IgG level ( J:187766 )

• 28-32 week old mutants exhibit hypergammaglobulinemia

• however levels of IgM are normal

increased IgG1 level ( J:187766 )

increased IgG2c level ( J:187766 )

renal/urinary system

abnormal renal glomerulus morphology ( J:187766 )

• mutants exhibit elevated IgG deposition within the kidney glomeruli

• however, renal failure is not seen in mutants up to 12 months of age

abnormal glomerular capillary morphology ( J:187766 )

• kidneys show occasional obstruction of the capillary lumina

increased mesangial cell number ( J:187766 )

• kidneys show moderate hypercellularity of the glomerular mesangium and occasional obstruction of the capillary lumina, however no signs of mononuclear cell infiltrates or signs of tubulointerstitial disease

cardiovascular system

abnormal glomerular capillary morphology ( J:187766 )

• kidneys show occasional obstruction of the capillary lumina

growth/size/body

enlarged spleen ( J:187766 )

• in 32-40 week old mutants

increased spleen weight ( J:187766 )

• in 32-40 week old mutants

spleen hyperplasia ( J:187766 )

• in 32-40 week old mutants

cellular

increased mesangial cell number ( J:187766 )

• kidneys show moderate hypercellularity of the glomerular mesangium and occasional obstruction of the capillary lumina, however no signs of mononuclear cell infiltrates or signs of tubulointerstitial disease

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:187766

Genotype
MGI:5439184

hm2

• Allelic Composition: Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix
• Genetic Background: C.129-Traf3ip2^tm1.1Lix

mortality/aging

premature death ( J:138560 )

• mutants begin to die around 4 months of age and by 12 months of age, about 83% mutants are dead

immune system

increased transitional stage B cell number ( J:138560 )

increased follicular B cell number ( J:138560 )

increased marginal zone B cell number ( J:138560 )

enlarged submandibular lymph nodes ( J:138560 )

• lymph nodes proximal to the submaxillary glands are greatly enlarged

increased autoantibody level ( J:138560 )

• mutants, but not wild-type mice, develop anti-SSA/Ro and anti-SSB/La autoantibodies in response to recombinant SSA/Ro and SSB/La antigens

increased inflammatory response ( J:138560 )

• lymphocyte infiltration in lacrimal, parotid and submaxillary glands; most infiltrates are in the perivascular or periductal areas of the glands

parotid gland inflammation ( J:138560 )

• lymphocyte infiltration in parotid glands

submandibular gland inflammation ( J:138560 )

• lymphocyte infiltration in submandibular glands

stomatitis ( J:138560 )

• mouth inflammation

lacrimal gland inflammation ( J:138560 )

• lymphocyte infiltration in lacrimal glands

• lacrimal glands are infiltrated by B220+ B cells and T cells

blepharitis ( J:138560 )

• some mutants develop skin lesions around the eyes due to excessive scratching of affected eyes

• both males and females exhibit difficulties in maintaining fully opened eyelids beginning around 3 weeks of age due to inflammation

kidney inflammation ( J:138560 )

• mutants at 8-12 months of age exhibit lymphocyte infiltration in the kidney, including the glomeruli

glomerulonephritis ( J:138560 )

• presence of anti-DNA autoantibodies and IgG complex in glomeruli, indicating development of glomerulonephritis

digestive/alimentary system

xerostomia ( J:138560 )

• mutants exhibit reduced flow rate of saliva production

increased submandibular gland size ( J:138560 )

• enlarged submaxillary glands

parotid gland inflammation ( J:138560 )

• lymphocyte infiltration in parotid glands

submandibular gland inflammation ( J:138560 )

• lymphocyte infiltration in submandibular glands

stomatitis ( J:138560 )

• mouth inflammation

renal/urinary system

kidney inflammation ( J:138560 )

• mutants at 8-12 months of age exhibit lymphocyte infiltration in the kidney, including the glomeruli

glomerulonephritis ( J:138560 )

• presence of anti-DNA autoantibodies and IgG complex in glomeruli, indicating development of glomerulonephritis

renal glomerular immunoglobulin deposits ( J:138560 )

craniofacial

xerostomia ( J:138560 )

• mutants exhibit reduced flow rate of saliva production

endocrine/exocrine glands

xerostomia ( J:138560 )

• mutants exhibit reduced flow rate of saliva production

parotid gland inflammation ( J:138560 )

• lymphocyte infiltration in parotid glands

submandibular gland inflammation ( J:138560 )

• lymphocyte infiltration in submandibular glands

abnormal exocrine gland morphology ( J:138560 )

• exocrine glands are infiltrated by large number of B and T cells

increased submandibular gland size ( J:138560 )

• enlarged submaxillary glands

lacrimal gland inflammation ( J:138560 )

• lymphocyte infiltration in lacrimal glands

• lacrimal glands are infiltrated by B220+ B cells and T cells

hematopoietic system

increased transitional stage B cell number ( J:138560 )

increased follicular B cell number ( J:138560 )

increased marginal zone B cell number ( J:138560 )

vision/eye

lacrimal gland inflammation ( J:138560 )

• lymphocyte infiltration in lacrimal glands

• lacrimal glands are infiltrated by B220+ B cells and T cells

blepharitis ( J:138560 )

• some mutants develop skin lesions around the eyes due to excessive scratching of affected eyes

• both males and females exhibit difficulties in maintaining fully opened eyelids beginning around 3 weeks of age due to inflammation

dry eyes ( J:138560 )

homeostasis/metabolism

xerostomia ( J:138560 )

• mutants exhibit reduced flow rate of saliva production

growth/size/body

xerostomia ( J:138560 )

• mutants exhibit reduced flow rate of saliva production

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:138560

Genotype
MGI:3511165

hm3

• Allelic Composition: Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix
• Genetic Background: involves: 129/Sv * BALB/c

hematopoietic system

enlarged spleen ( J:93923 )

increased dendritic cell number ( J:93923 )

• the number of dendritic cells is increased in the spleen

increased B cell number ( J:93923 )

• the total splenic B cell population is increased however the proportions of different B cell stages are the same as in wild-type littermates

abnormal spleen B cell corona morphology ( J:93923 )

• the density of B cell zones is increased

increased immunoglobulin level ( J:93923 )

increased IgE level ( J:93923 )

increased IgG level ( J:93923 )

• IgG subclasses except for IgG3 are increased

• both T cell dependent and independent antigens elicit increased antigen-specific responses

immune system

abnormal immune system morphology ( J:93923 )

enlarged spleen ( J:93923 )

increased dendritic cell number ( J:93923 )

• the number of dendritic cells is increased in the spleen

increased B cell number ( J:93923 )

• the total splenic B cell population is increased however the proportions of different B cell stages are the same as in wild-type littermates

abnormal spleen B cell corona morphology ( J:93923 )

• the density of B cell zones is increased

enlarged lymph nodes ( J:93923 )

• at 3 weeks of age the lymph nodes are enlarged from lymphoid hyperplasia, increased germinal centers, and accumulation of plasma cells

lymphoid hyperplasia ( J:93923 )

abnormal immune system physiology ( J:93923 )

increased immunoglobulin level ( J:93923 )

increased IgE level ( J:93923 )

increased IgG level ( J:93923 )

• IgG subclasses except for IgG3 are increased

• both T cell dependent and independent antigens elicit increased antigen-specific responses

increased autoantibody level ( J:93923 )

increased anti-double stranded DNA antibody level ( J:93923 )

• anti-dsDNA IgG antibodies are detected

increased anti-histone antibody level ( J:93923 )

• anti-histone IgG antibodies are detected

increased anti-single stranded DNA antibody level ( J:93923 )

• anti-ssDNA IgG antibodies are detected

increased inflammatory response ( J:93923 )

• inflammation is seen in multiple tissues including the skin

respiratory system inflammation ( J:93923 )

• upper respiratory airway inflammation is seen

respiratory system

respiratory system inflammation ( J:93923 )

• upper respiratory airway inflammation is seen

growth/size/body

enlarged spleen ( J:93923 )

Genotype
MGI:3511174

cn4

• Allelic Composition: Traf3ip2^tm1Lix/Traf3ip2^tm1.1Lix; Tg(CD19-cre/ERT2)1Cgn/0
• Genetic Background: involves: 129/Sv * BALB/c

hematopoietic system

enlarged spleen ( J:93923 )

• this is less severe than in Act1 null mice

increased dendritic cell number ( J:93923 )

• the number of dendritic cells is increased in the spleen, this is less severe than in Act1 null mice

increased B cell number ( J:93923 )

• the total splenic B cell population is increased however the proportions of different B cell stages are the same as in wild-type littermates

• this is less severe than in Act1 null mice

increased immunoglobulin level ( J:93923 )

• this is less severe than in Act1 null mice

immune system

enlarged spleen ( J:93923 )

• this is less severe than in Act1 null mice

increased dendritic cell number ( J:93923 )

• the number of dendritic cells is increased in the spleen, this is less severe than in Act1 null mice

increased B cell number ( J:93923 )

• the total splenic B cell population is increased however the proportions of different B cell stages are the same as in wild-type littermates

• this is less severe than in Act1 null mice

increased immunoglobulin level ( J:93923 )

• this is less severe than in Act1 null mice

enlarged lymph nodes ( J:93923 )

• this is less severe than in Act1 null mice

growth/size/body

enlarged spleen ( J:93923 )

• this is less severe than in Act1 null mice

Genotype
MGI:5440219

cx5

• Allelic Composition: Tcrb^tm1Mom/Tcrb^tm1Mom; Tcrd^tm1Mom/Tcrd^tm1Mom; Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix
• Genetic Background: B6.129-Tcrb^tm1Mom Traf3ip2^tm1.1Lix Tcrd^tm1Mom

immune system

immune system phenotype ( J:187766 )

N • triple mutants exhibit reduced lupus-like phenotypes compared to Traf3ip2 single homozygotes, with normal spleen weight and cellularity, normal B cell numbers (B cell numbers however are decreased compared to Tcrb and Tcrd double homozygous mutants), normal cervical lymph node weight and cellularity, significantly less total IgG antibodies and anti-nuclear antigen specific IgG autoantibodies, and no IgG deposition in the kidney glomeruli

increased immature B cell number ( J:187766 )

• 16-18 week old mutants exhibit a trend toward an increase in numbers of immature B cells

abnormal transitional stage B cell morphology ( J:187766 )

• ratios of T2:T1 and T3:T1 B cells are increased compared to wild-type mice

increased marginal zone B cell number ( J:187766 )

• mutants exhibit increased levels of marginal zone B cells compared to wild-type mice, however levels are similar to that seen in Traf3ip2 single homozygotes or to Tcrb and Tcrd double homozygous mutants, indicating no further increase in levels

decreased T cell number ( J:187766 )

• decrease in the number of T cells in the spleen compared to wild-type mice and Traf3ip2 single homozygotes

decreased IgG level ( J:187766 )

• mutants develop significantly less total IgG antibodies (IgG, IgG1, IgG2c) and anti-nuclear antigen specific IgG autoantibodies than Traf3ip2 single homozygotes

• the IgG deposition within the kidney glomeruli that is seen in Traf3ip2 single homozygotes is not seen in triple mutants

increased IgM level ( J:187766 )

• mutants exhibit elevated levels of IgM deposition within kidney glomeruli

• serum levels of anti-chromatin IgM, anti-histone IgM, and anti-dsDNA Igm are elevated in triple mutants compared to Traf3ip2 single homozygotes

increased autoantibody level ( J:187766 )

increased anti-chromatin antibody level ( J:187766 )

• serum levels of anti-chromatin IgM are elevated in triple mutants compared to Traf3ip2 single homozygotes

increased anti-double stranded DNA antibody level ( J:187766 )

• serum levels anti-dsDNA IgM are elevated in triple mutants compared to Traf3ip2 single homozygotes

increased anti-histone antibody level ( J:187766 )

• serum levels of anti-histone IgM are elevated in triple mutants compared to Traf3ip2 single homozygotes

hematopoietic system

increased immature B cell number ( J:187766 )

• 16-18 week old mutants exhibit a trend toward an increase in numbers of immature B cells

abnormal transitional stage B cell morphology ( J:187766 )

• ratios of T2:T1 and T3:T1 B cells are increased compared to wild-type mice

increased marginal zone B cell number ( J:187766 )

• mutants exhibit increased levels of marginal zone B cells compared to wild-type mice, however levels are similar to that seen in Traf3ip2 single homozygotes or to Tcrb and Tcrd double homozygous mutants, indicating no further increase in levels

decreased T cell number ( J:187766 )

• decrease in the number of T cells in the spleen compared to wild-type mice and Traf3ip2 single homozygotes

decreased IgG level ( J:187766 )

• mutants develop significantly less total IgG antibodies (IgG, IgG1, IgG2c) and anti-nuclear antigen specific IgG autoantibodies than Traf3ip2 single homozygotes

• the IgG deposition within the kidney glomeruli that is seen in Traf3ip2 single homozygotes is not seen in triple mutants

increased IgM level ( J:187766 )

• mutants exhibit elevated levels of IgM deposition within kidney glomeruli

• serum levels of anti-chromatin IgM, anti-histone IgM, and anti-dsDNA Igm are elevated in triple mutants compared to Traf3ip2 single homozygotes

cardiovascular system

abnormal glomerular capillary morphology ( J:187766 )

• kidneys show occasional obstruction of the capillary lumina

renal/urinary system

abnormal glomerular capillary morphology ( J:187766 )

• kidneys show occasional obstruction of the capillary lumina

increased mesangial cell number ( J:187766 )

• kidneys show moderate hypercellularity of the glomerular mesangium and occasional obstruction of the capillary lumina, however no signs of mononuclear cell infiltrates or signs of tubulointerstitial disease

renal glomerular immunoglobulin deposits ( J:187766 )

• mutants exhibit elevated levels of IgM deposition within kidney glomeruli

cellular

increased mesangial cell number ( J:187766 )

• kidneys show moderate hypercellularity of the glomerular mesangium and occasional obstruction of the capillary lumina, however no signs of mononuclear cell infiltrates or signs of tubulointerstitial disease

Genotype
MGI:3511170

cx6

• Allelic Composition: Cd40^tm1Kik/Cd40^tm1Kik; Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix
• Genetic Background: involves: 129 * 129P2/OlaHsd * BALB/c

hematopoietic system

enlarged spleen ( J:93923 )

• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes

• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes

increased transitional stage B cell number ( J:138560 )

• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes

increased follicular B cell number ( J:138560 )

• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes

increased marginal zone B cell number ( J:138560 )

• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes

abnormal B cell physiology ( J:138560 )

• Tnfsf13b (BAFF) stimulation results in enhanced B cell survival compared to single Cd40 mutants

immune system

immune system phenotype ( J:138560 )

N • double mutants do not exhibit production of anti-SSA/Ro and anti-SSB/La autoantibodies in response to recombinant SSA/Ro and SSB/La antigens, as seen in Traf3ip2 single homozygotes

enlarged spleen ( J:93923 )

• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes

• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes

increased transitional stage B cell number ( J:138560 )

• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes

increased follicular B cell number ( J:138560 )

• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes

increased marginal zone B cell number ( J:138560 )

• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes

abnormal B cell physiology ( J:138560 )

• Tnfsf13b (BAFF) stimulation results in enhanced B cell survival compared to single Cd40 mutants

enlarged lymph nodes ( J:93923 )

• enlargement of the lymph nodes is reduced compared to Traf3ip2 single homozygotes

growth/size/body

enlarged spleen ( J:93923 )

• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes

• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes

Genotype
MGI:3511169

cx7

• Allelic Composition: Traf3ip2^tm1.1Lix/Traf3ip2^tm1.1Lix; Tnfsf13b^tm1Msc/Tnfsf13b^tm1Msc
• Genetic Background: involves: 129 * 129S2/SvPas * BALB/c

hematopoietic system

enlarged spleen ( J:93923 )

• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes

• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes

decreased B cell number ( J:138560 )

• total splenic B cells, transitional B cells and follicular B cells are reduced in the spleen

decreased transitional stage B cell number ( J:138560 )

decreased mature B cell number ( J:138560 )

• total number of mature B cells is reduced

decreased follicular B cell number ( J:138560 )

immune system

enlarged spleen ( J:93923 )

• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes

• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes

decreased B cell number ( J:138560 )

• total splenic B cells, transitional B cells and follicular B cells are reduced in the spleen

decreased transitional stage B cell number ( J:138560 )

decreased mature B cell number ( J:138560 )

• total number of mature B cells is reduced

decreased follicular B cell number ( J:138560 )

enlarged lymph nodes ( J:93923 )

• enlargement of the lymph nodes is reduced compared to Traf3ip2 single homozygotes

increased autoantibody level ( J:138560 )

• mutants develop anti-SSA/Ro and anti-SSB/La autoantibodies in response to recombinant SSA/Ro and SSB/La antigens, although to a lower level than in Traf3ip2 single homozygotes due to the low number of B cells, but higher levels than in Tnfsf13b single homozygotes

growth/size/body

enlarged spleen ( J:93923 )

• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes

• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes