Analysis Tools
mortality/aging
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• mean age of death in females was 17 weeks of age
(J:13757)
• mean age of death in males was 22 weeks of age
(J:13757)
• 50% mortality is observed at 5 or 5.5 months for females and males with 90% mortality at 7.3 or 8.6 months in females and males
(J:27634)
• life span of females is 120+/-4 days
(J:28885)
• life span of males is 154+/-32 days
(J:28885)
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immune system
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• frequency of C3d receptor bearing cells declines with age
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• Anti-dsDNA B cells escape receptor editing
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• lymph node cells (T cell origin) are abnormal; cells are Ly-2-/L3T4-/surface Ig-
(J:8267)
• increase in T-cell frequencies and absolute numbers with advanced disease; however, the number of Ly123+ and Ly23+ T cells is markedly decreased in older mice compared to young mice
(J:108760)
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• increase in thymus weight restricted to the medulla
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• slighlty enlarged
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• doubling of thymus weight
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• thymic atrophy is observed; severity is most severe in the cortex but usually involves the medulla in most animals
• initial lesion is loss of cortical thymocytes, with later degeneration (cystic) of thymocytes of medulla
• in 5-10% of animals, there is medullary or stromal hyperplasia that maintains or increases the size of the thymus
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• atrophic cortex
(J:13757)
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• spleen is 7-fold larger than controls
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• mice have a larger marginal zone B cell population (10.8% of splenic lymphocytes) compared to BALB/c controls (1.9%)
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• slight enlargement
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• in mice with lymph node hyperplasia, larger nodes show extensive hemorrhage and cystic necrosis, which results in clinically observed terminal reduction in size
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• in mice with lymph node hyperplasia, larger nodes show extensive cystic necrosis
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• mice show 4- to 6-fold higher frequencies of immunoglobulin-secreting cells (IgSC) compared to normal controls
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• enlargement started at 8 weeks of age and progressed until lymph node weights were 100 times control lymph node weight by 16 weeks of age
(J:13757)
• node architecture was blurred, with proliferation of lymphocytes with some admixture of plasma cells and histiocytes
(J:13757)
• no evidence of malignancy was present, despite enlargement
(J:13757)
• all mice begin to develop generalized lymph lymphadenopathy when >3 months of age; in about 33%. lymph nodes shrink markedly 7-10 days before death
(J:27634)
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• lymph nodes are up to 100 times normal size
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• in mice with lymph node hyperplasia, larger nodes show extensive hemorrhage
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• arteritis is observed in a number of organs, and is associated with hemorrhage and infarcts in the lymph nodes
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• lymphocytic infiltration and lymphocytic foci are observed in mice 3.4-3.7 months of age
• treatment with danazol or Org 4094 sifnificantly lowers number of foci and percentage of lymphocyte infiltration, as well as other immune parameters compared to untreated controls
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• autoimmune sialodenitis with parenchymal destruction is observed in 4-6 month old mice in submandibular salivary glands of female mice
• most infiltrating cells are CD4+ and Vbeta8+ with a minority being CD4+ and Vbeta6+
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• animals display thyroid gland infiltration (autoimmune thyroiditis)
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• adult lacrimal glands show infiltration by lymphocytes
• treatment with steroids alleviates lymphocyte infiltration
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• mice show 4- to 6-fold higher frequencies of immunoglobulin-secreting cells in spleens compared to normal controls
(J:6257)
• hypergammaglobulinemia
(J:13757)
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• 2-fold increase
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• at 2-3 months, concentration are up to 5 times control and 8 times control at 5 months
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• 10-fold increase
(J:28885)
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• 10-fold increase
(J:28885)
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• 2-fold increase
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• 2-fold increase
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• cells do not generate CTL in response to stimulation with alloantigens
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• cells do not proliferate in response to stimulation with alloantigens
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• activity of helper T cells is enhanced in older mice relative to younger animals or normal controls
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• 4-6 month old mice exhibit significantly depressed cytotoxic T cell response to alloantigens
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• stimulation with concanavalin A does not induce cells to produce Il2
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• perivascular infiltration of lymphocytes, plasma cells, and histiocytes in lung, kidney, salivary gland and liver
• perivascular and peribronchial lymphoproliferation observed in lung reslting in patches of atelectasis and exudate containing patches
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• early in life, mice show reduced Il2 production, that worsens with age, such that almost no Il2 activity is detected in culture supernatants from 2 month old animals; spleen cells show no stimulated Il2 production upon stimulation with concanavalin A
(J:6638)
• mice have severe deficiency in Il-2 production
(J:7488)
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• thymocytoxic autoantibodies are detected with aging
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• levels reach 4 and 11% in males and females
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• anti-Sm antibodies are detected in males and females but not in controls
(J:27634)
• anti-nuclear antigen antibody (ANA) activity in renal eluate Ig is much higher than activity in serum Ig for anti-ssDNA and anti-dsDNA
(J:27634)
• antinuclear antibody titers are detectable at 8 weeks of age and increased rapidly
(J:28885)
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• 4-month old mice show around 4-fold higher number of spleen cells secreting autoantibodies to dsDNA compared to 8-month old wild-type controls.
(J:6257)
• high levels detected at 4-5 months
(J:27634)
• significant levels of IgM and IgG antibodies that bind dsDNA antibodies are detected in mice 6-8 weeks of age
(J:131138)
• levels of these auto antibodies rise with age
(J:131138)
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• detected at significant levels at 2 months, with very high levels detected at 4-5 months
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• immune complex glomerulonephritis
(J:13757)
• mice show a largely subacute proliferative form of disease; lesions involve proliferation of endothelial and mesangial cells
(J:27634)
• glomerular lesions involve proliferation of both endothelial and mesangial cells and basement membrane thickening
(J:28885)
• granular deposits of immunoglobulins present in the capillary walls
(J:28885)
• capsular cell proliferation, tubular damage, and casts were seen in severe lesions
(J:28885)
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renal/urinary system
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• granular deposits of immunoglobulins present in the capillary walls
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• proliferation of endothelial cells
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• proliferation of mesangial cells
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• glomerular lesions involve proliferation of endothelial and mesangial cells
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• incomplete penetrance, 50% of females tested have a 9-fold increase over controls
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• immune complex glomerulonephritis
(J:13757)
• mice show a largely subacute proliferative form of disease; lesions involve proliferation of endothelial and mesangial cells
(J:27634)
• glomerular lesions involve proliferation of both endothelial and mesangial cells and basement membrane thickening
(J:28885)
• granular deposits of immunoglobulins present in the capillary walls
(J:28885)
• capsular cell proliferation, tubular damage, and casts were seen in severe lesions
(J:28885)
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• glomerular basement membrane thickening
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• capsular cell proliferation is seen in severe glomerular lesions
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• between 2 and 5 months, granular IgG and C3 deposits increase in capillary wall and mesangium
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renal cast
(
J:28885
)
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• casts were seen in severe glomerular lesions
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homeostasis/metabolism
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• mice have high concentrations of circulating immune complex at 2-3 and 4-5 months
• high levels of cyroglobulins are found in mice at 5 months
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• total serum protein levels are slightly increased
• 2-fold increase in beta- and 5-fold increase in gamma-globulins
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• 20-25% of old, diseased mice show joint swelling of the hind feet and lower legs; involving destruction of articular cartilage, proliferation of synovium, pannus formations, and sometimes joint effusions
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• stimulation with concanavalin A does not induce cells to produce Il2
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• incomplete penetrance, 50% of females tested have a 9-fold increase over controls
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hematopoietic system
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• increase in thymus weight restricted to the medulla
|
|
• slighlty enlarged
|
|
• doubling of thymus weight
|
|
• thymic atrophy is observed; severity is most severe in the cortex but usually involves the medulla in most animals
• initial lesion is loss of cortical thymocytes, with later degeneration (cystic) of thymocytes of medulla
• in 5-10% of animals, there is medullary or stromal hyperplasia that maintains or increases the size of the thymus
|
|
• atrophic cortex
(J:13757)
|
|
• spleen is 7-fold larger than controls
|
|
• frequency of C3d receptor bearing cells declines with age
|
|
• Anti-dsDNA B cells escape receptor editing
|
|
• mice have a larger marginal zone B cell population (10.8% of splenic lymphocytes) compared to BALB/c controls (1.9%)
|
|
• lymph node cells (T cell origin) are abnormal; cells are Ly-2-/L3T4-/surface Ig-
(J:8267)
• increase in T-cell frequencies and absolute numbers with advanced disease; however, the number of Ly123+ and Ly23+ T cells is markedly decreased in older mice compared to young mice
(J:108760)
|
|
• mice show 4- to 6-fold higher frequencies of immunoglobulin-secreting cells in spleens compared to normal controls
(J:6257)
• hypergammaglobulinemia
(J:13757)
|
|
• 2-fold increase
|
|
• at 2-3 months, concentration are up to 5 times control and 8 times control at 5 months
|
|
• 10-fold increase
(J:28885)
|
|
• 10-fold increase
(J:28885)
|
|
• 2-fold increase
|
|
• 2-fold increase
|
|
• cells do not generate CTL in response to stimulation with alloantigens
|
|
• cells do not proliferate in response to stimulation with alloantigens
|
|
• activity of helper T cells is enhanced in older mice relative to younger animals or normal controls
|
|
• 4-6 month old mice exhibit significantly depressed cytotoxic T cell response to alloantigens
|
cardiovascular system
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• granular deposits of immunoglobulins present in the capillary walls
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• proliferation of endothelial cells
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• 15-30% of mice suffer old and/or acute myocardial infarction involving either ventricle and judged severe enough to contribute to death
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• in mice with lymph node hyperplasia, larger nodes show extensive hemorrhage
|
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• arteritis is observed in a number of organs, and is associated with hemorrhage and infarcts in the lymph nodes
|
endocrine/exocrine glands
| N |
• lymphatic tissues that undergo age-related increase in weight due to lymphocytic accumulation are decreased in weight with cyclophosphamide treatment compared to placebo treated controls
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• lymphocytic infiltration and lymphocytic foci are observed in mice 3.4-3.7 months of age
• treatment with danazol or Org 4094 sifnificantly lowers number of foci and percentage of lymphocyte infiltration, as well as other immune parameters compared to untreated controls
|
|
• autoimmune sialodenitis with parenchymal destruction is observed in 4-6 month old mice in submandibular salivary glands of female mice
• most infiltrating cells are CD4+ and Vbeta8+ with a minority being CD4+ and Vbeta6+
|
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• dexamethasone treatment increases weight of lacrimal tissue compared to untreated mice; treatment results in a reduction in tear volume
|
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• treatment with androgens increases gland weight in mutants
• this treatment significantly decreases lymphocytic infiltration into submandibular glands
|
|
• increase in thymus weight restricted to the medulla
|
|
• slighlty enlarged
|
|
• doubling of thymus weight
|
|
• thymic atrophy is observed; severity is most severe in the cortex but usually involves the medulla in most animals
• initial lesion is loss of cortical thymocytes, with later degeneration (cystic) of thymocytes of medulla
• in 5-10% of animals, there is medullary or stromal hyperplasia that maintains or increases the size of the thymus
|
|
• atrophic cortex
(J:13757)
|
|
• inflamed tissue has massive infiltration organized into lymphoid follicle centers and extensive interstitially distributed lymphocytes
• fibrosis is minimal, with only 1% of tissue displaying fibroblast growth; when detected, fibrosis is adjacent to atrophic follicles
• functional communication between cells in thyroid cell cultures is dramatically reduced
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• marked decrease in follicle size is noted proceeding from center of lobe toward periphery
|
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• animals display thyroid gland infiltration (autoimmune thyroiditis)
|
|
• adult lacrimal glands show infiltration by lymphocytes
• treatment with steroids alleviates lymphocyte infiltration
|
skeleton
|
• 20-25% of old, diseased mice show joint swelling of the hind feet and lower legs; involving destruction of articular cartilage, proliferation of synovium, pannus formations, and sometimes joint effusions
|
digestive/alimentary system
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• treatment with androgens increases gland weight in mutants
• this treatment significantly decreases lymphocytic infiltration into submandibular glands
|
|
• lymphocytic infiltration and lymphocytic foci are observed in mice 3.4-3.7 months of age
• treatment with danazol or Org 4094 sifnificantly lowers number of foci and percentage of lymphocyte infiltration, as well as other immune parameters compared to untreated controls
|
|
• autoimmune sialodenitis with parenchymal destruction is observed in 4-6 month old mice in submandibular salivary glands of female mice
• most infiltrating cells are CD4+ and Vbeta8+ with a minority being CD4+ and Vbeta6+
|
vision/eye
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• adult lacrimal glands show infiltration by lymphocytes
• treatment with steroids alleviates lymphocyte infiltration
|
integument
skin lesions
(
J:28885
)
|
• lesions accompanied by hair loss and scab formation were common
• erythemateous lesions of the ear often become necrotic
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cellular
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• proliferation of mesangial cells
|
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• in mice with lymph node hyperplasia, larger nodes show extensive cystic necrosis
|
|
• cells do not proliferate in response to stimulation with alloantigens
|
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• glomerular lesions involve proliferation of endothelial and mesangial cells
|
growth/size/body
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• spleen is 7-fold larger than controls
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autoimmune lymphoproliferative syndrome | DOID:6688 |
OMIM:601859 |
J:28885 | |
| Sjogren's syndrome | DOID:12894 |
OMIM:270150 |
J:1028 , J:18512 , J:21965 | |
| 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:27634 , J:28885 , J:108760 , J:131138 | |
