Mouse Genome Informatics
hm1
    Pdcd1tm1Hon/Pdcd1tm1Hon
B6.129S2-Pdcd1tm1Hon
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• increased layers of synovial tissues in foot joints at 6 months of age
• arthritic lesions more pronounced at 14 months of age
• mild proliferative glomerulonephritis at 6 months age
• less than 50% of glomeruli affected
• by 14 months, 50% of mice with a lupus-like glomerulonephritis
• only about 80% of mice show long term MHC class II mismatch allograft survival (Bm12 into B6) compared to about 100% survival in wild-type mice
• however, survival time of MHC class I mismatch allografts is the same as wild-type controls

renal/urinary system
• mild proliferative glomerulonephritis at 6 months age
• less than 50% of glomeruli affected
• by 14 months, 50% of mice with a lupus-like glomerulonephritis

skeleton
• increased layers of synovial tissues in foot joints at 6 months of age
• arthritic lesions more pronounced at 14 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus, Susceptibility to, 2; SLEB2 605218 J:78802


Mouse Genome Informatics
hm2
    Pdcd1tm1Hon/Pdcd1tm1Hon
BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• start to die around 5 weeks of age, 2/3 are dead by 30 weeks

cardiovascular system
• massively enlarged hearts at death
• thin right venricular wall
• both ventricles dilated to about 2X normal diameter
• sporatic fibrosis and scar formation
• impaired pump function of the heart
• reduced movement of the ventricular walls and interventricular septum

immune system
• higher titers of autoantibodies (IgG1)
• deposition of IgG and C3 complement around cardiomyocytes

liver/biliary system
• varying degrees of hepatomegaly

muscle
• reduced movement of the ventricular walls and interventricular septum

vision/eye
• protrusion of eyeballs occurs a few weeks before death

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus, Susceptibility to, 2; SLEB2 605218 J:66979


Mouse Genome Informatics
hm3
    Pdcd1tm1Hon/Pdcd1tm1Hon
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• lymphoid cells in the peritoneal cavity increased about 2 fold
• increased numbers of B cells in the spleen
• B1 cells in the peritoneal cavity are increased
• proliferative response of B cells to anti-IgM is greatly enhanced
• myeloid lineages in the spleen are also increased
• moderate splenomegaly
• increased T cell independent antigen responses
• T cell dependent antigen responses were normal
• IgG2b levels were increased
• IgG3 levels were 3X normal

immune system
• lymphoid cells in the peritoneal cavity increased about 2 fold
• increased numbers of B cells in the spleen
• B1 cells in the peritoneal cavity are increased
• proliferative response of B cells to anti-IgM is greatly enhanced
• myeloid lineages in the spleen are also increased
• moderate splenomegaly
• increased T cell independent antigen responses
• T cell dependent antigen responses were normal
• IgG2b levels were increased
• IgG3 levels were 3X normal

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus, Susceptibility to, 2; SLEB2 605218 J:50688


Mouse Genome Informatics
cx4
    Btlatm1Kmm/Btlatm1Kmm
Pdcd1tm1Hon/Pdcd1tm1Hon

B6.129S-Pdcd1tm1Hon Btlatm1Kmm
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• increase in proliferation in response to fully MHC-mismatched stimulation
• increase is decreased by rapamycin treatment
• decreased survival time of cardiac allografts (source strain Bm12; 10.5 +/- 1.5 days) compared to mice homozygous for the Btla allele alone (14.3 +/- 3.8 days) or wild-type mice (over 100 days)

hematopoietic system
• increase in proliferation in response to fully MHC-mismatched stimulation
• increase is decreased by rapamycin treatment


Mouse Genome Informatics
cx5
    Pdcd1tm1Hon/Pdcd1tm1Hon
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• in conjunction with anti-CTLA-4 antibody treatment, mice exhibit reduced paralysis induced by experimental autoimmune encephalomyelitis (EAE) compared to wild type mice
• however, adoptive transfer of Gt(ROSA)26Sortm2Awai Cd19tm1(cre)Cgn double heterozygous B cells increases paralysis induced by EAE despite treatment with anti-CTLA-4 antibodies compared to wild-type mice receiving Gt(ROSA)26Sortm2Awai Cd19tm1(cre)Cgn double heterozygous B cells


Mouse Genome Informatics
cx6
    Fcgr2btm1Ttk/Fcgr2btm1Ttk
Pdcd1tm1Hon/Pdcd1tm1Hon

involves: 129S2/SvPas * 129S4/SvJae * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• inflammatory cytokines, including Il2ra, Tnf, Icos, Il1b, Socs1, and Vcam1, are expressed in the suburothelial layer of mice that have anti-urothelial antibodies
• urinary cytokines, including, GM-CSF, TNF-alpha, IL1-alpha, G-CSF, IL-1beta, are upregulated in the urine of mice that have anti-urothelial antibodies
• anti-urothelial autoantibodies are seen in the serum as early as 7 weeks of age, with about 50% of mice showing autoantibodies at 10 weeks of age
• mice that are positive for anti-urothelial antibodies show massive infiltration of inflammatory cells at the suburothelial layer

renal/urinary system
• mice that are positive for anti-urothelial antibodies show massive infiltration of inflammatory cells at the suburothelial layer
• mice that are positive for anti-urothelial antibodies show disarrangement of urothelial plaque on the surface of the bladder and disarranged cellular structure of the bladder epithelium at 16 weeks of age
• surface of bladder epithelium shows poorer plaque formation, exposing bare surface of smaller epithelial cells beneath it, in mice that are positive for anti-urothelial antibodies
• mice that are positive for anti-urothelial antibodies void less urine per void than wild-type mice, even when corrected for body weight

homeostasis/metabolism
• inflammatory cytokines, including Il2ra, Tnf, Icos, Il1b, Socs1, and Vcam1, are expressed in the suburothelial layer of mice that have anti-urothelial antibodies
• urinary cytokines, including, GM-CSF, TNF-alpha, IL1-alpha, G-CSF, IL-1beta, are upregulated in the urine of mice that have anti-urothelial antibodies

growth/size/body
• lower body weight in mice that are positive for anti-urothelial antibodies