Mouse Genome Informatics
hm1
    Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix
B6.129-Traf3ip2tm1.1Lix
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
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 (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
• 16-18 week old mutants exhibit significantly increased numbers of total immature AA4.1+B220+ B cells
• mutants exhibit elevated levels of marginal zone B cells
• however, no increase in the number of follicular mature B cells is seen
• 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
• in 32-40 week old mutants
• in 32-40 week old mutants
• in 32-40 week old mutants
• 28-32 week old mutants exhibit hypergammaglobulinemia
• however levels of IgM are normal
• increase in cervical lymph node weight and cellularity in 32-40 week old mutants
• increase in cervical lymph node weight and cellularity in 32-40 week old mutants
• 28-32 week old mutants exhibit elevated levels of serum anti-nuclear autoantibodies (anti-chromatin IgG, anti-histone IgG, and anti-dsDNA IgG)

hematopoietic system
• 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
• 16-18 week old mutants exhibit significantly increased numbers of total immature AA4.1+B220+ B cells
• mutants exhibit elevated levels of marginal zone B cells
• however, no increase in the number of follicular mature B cells is seen
• 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
• in 32-40 week old mutants
• in 32-40 week old mutants
• in 32-40 week old mutants
• 28-32 week old mutants exhibit hypergammaglobulinemia
• however levels of IgM are normal

renal/urinary system
• mutants exhibit elevated IgG deposition within the kidney glomeruli
• however, renal failure is not seen in mutants up to 12 months of age
• kidneys show occasional obstruction of the capillary lumina
• 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
• kidneys show occasional obstruction of the capillary lumina

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus; SLE 152700 J:187766


Mouse Genome Informatics
hm2
    Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix
C.129-Traf3ip2tm1.1Lix
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants begin to die around 4 months of age and by 12 months of age, about 83% mutants are dead

immune system
• lymph nodes proximal to the submaxillary glands are greatly enlarged
• 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
• lymphocyte infiltration in lacrimal, parotid and submaxillary glands; most infiltrates are in the perivascular or periductal areas of the glands
• lymphocyte infiltration in submandibular glands
• lymphocyte infiltration in lacrimal glands
• lacrimal glands are infiltrated by B220+ B cells and T cells
• 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
• mutants at 8-12 months of age exhibit lymphocyte infiltration in the kidney, including the glomeruli
• presence of anti-DNA autoantibodies and IgG complex in glomeruli, indicating development of glomerulonephritis

digestive/alimentary system
• mutants exhibit reduced flow rate of saliva production
• lymphocyte infiltration in parotid glands
• enlarged submaxillary glands
• lymphocyte infiltration in submandibular glands

renal/urinary system
• mutants at 8-12 months of age exhibit lymphocyte infiltration in the kidney, including the glomeruli
• presence of anti-DNA autoantibodies and IgG complex in glomeruli, indicating development of glomerulonephritis

craniofacial
• mouth inflammation
• mutants exhibit reduced flow rate of saliva production

endocrine/exocrine glands
• mutants exhibit reduced flow rate of saliva production
• lymphocyte infiltration in submandibular glands
• exocrine glands are infiltrated by large number of B and T cells
• lymphocyte infiltration in parotid glands
• enlarged submaxillary glands
• lymphocyte infiltration in lacrimal glands
• lacrimal glands are infiltrated by B220+ B cells and T cells

hematopoietic system

vision/eye
• lymphocyte infiltration in lacrimal glands
• lacrimal glands are infiltrated by B220+ B cells and T cells
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:138560


Mouse Genome Informatics
hm3
    Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix
involves: 129/Sv * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• the number of dendritic cells is increased in the spleen
• the total splenic B cell population is increased however the proportions of different B cell stages are the same as in wild-type littermates
• the density of B cell zones is increased
• IgG subclasses except for IgG3 are increased
• both T cell dependent and independent antigens elicit increased antigen-specific responses

immune system
• the number of dendritic cells is increased in the spleen
• the total splenic B cell population is increased however the proportions of different B cell stages are the same as in wild-type littermates
• the density of B cell zones is increased
• at 3 weeks of age the lymph nodes are enlarged from lymphoid hyperplasia, increased germinal centers, and accumulation of plasma cells
• IgG subclasses except for IgG3 are increased
• both T cell dependent and independent antigens elicit increased antigen-specific responses
• anti-dsDNA IgG antibodies are detected
• anti-histone IgG antibodies are detected
• anti-ssDNA IgG antibodies are detected
• inflammation is seen in multiple tissues including the skin
• upper respiratory airway inflammation is seen

respiratory system
• upper respiratory airway inflammation is seen


Mouse Genome Informatics
cn4
    Traf3ip2tm1Lix/Traf3ip2tm1.1Lix
Tg(CD19-cre/ERT2)1Cgn/0

involves: 129/Sv * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• the number of dendritic cells is increased in the spleen, this is less severe than in Act1 null mice
• 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
• this is less severe than in Act1 null mice
• this is less severe than in Act1 null mice

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


Mouse Genome Informatics
cx5
    Tcrbtm1Mom/Tcrbtm1Mom
Tcrdtm1Mom/Tcrdtm1Mom
Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix

B6.129-Tcrbtm1Mom Traf3ip2tm1.1Lix Tcrdtm1Mom
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
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 (J:187766)
• 16-18 week old mutants exhibit a trend toward an increase in numbers of immature B cells
• 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
• decrease in the number of T cells in the spleen compared to wild-type mice and Traf3ip2 single homozygotes
• ratios of T2:T1 and T3:T1 B cells are increased compared to wild-type mice
• 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
• 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
• serum levels of anti-chromatin IgM are elevated in triple mutants compared to Traf3ip2 single homozygotes
• serum levels anti-dsDNA IgM are elevated in triple mutants compared to Traf3ip2 single homozygotes
• serum levels of anti-histone IgM are elevated in triple mutants compared to Traf3ip2 single homozygotes

hematopoietic system
• 16-18 week old mutants exhibit a trend toward an increase in numbers of immature B cells
• 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
• decrease in the number of T cells in the spleen compared to wild-type mice and Traf3ip2 single homozygotes
• ratios of T2:T1 and T3:T1 B cells are increased compared to wild-type mice
• 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
• 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
• kidneys show occasional obstruction of the capillary lumina

renal/urinary system
• mutants exhibit elevated levels of IgM deposition within kidney glomeruli
• kidneys show occasional obstruction of the capillary lumina
• 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 Genome Informatics
cx6
    Cd40tm1Kik/Cd40tm1Kik
Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix

involves: 129 * 129P2/OlaHsd * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes
• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes
• Tnfsf13b (BAFF) stimulation results in enhanced B cell survival compared to single Cd40 mutants

immune system
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 (J:138560)
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes
• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes
• Tnfsf13b (BAFF) stimulation results in enhanced B cell survival compared to single Cd40 mutants
• enlargement of the lymph nodes is reduced compared to Traf3ip2 single homozygotes

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Immunodeficiency with Hyper-IgM, Type 1; HIGM1 308230 J:93923


Mouse Genome Informatics
cx7
    Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix
Tnfsf13btm1Msc/Tnfsf13btm1Msc

involves: 129 * 129S2/SvPas * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• total splenic B cells, transitional B cells and follicular B cells are reduced in the spleen
• total number of mature B cells is reduced
• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes
• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes

immune system
• total splenic B cells, transitional B cells and follicular B cells are reduced in the spleen
• total number of mature B cells is reduced
• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes
• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes
• enlargement of the lymph nodes is reduced compared to Traf3ip2 single homozygotes
• 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