Analysis ToolsMouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | rheumatoid arthritis | DOID:7148 |
OMIM:180300 |
J:36815 |
|
Allele Symbol Allele Name Allele ID |
Tg(TcraR28,TcrbR28)KRNDim transgene insertion KRN, Diane Mathis MGI:3767242 |
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| Summary |
5 genotypes
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|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | rheumatoid arthritis | DOID:7148 |
OMIM:180300 |
J:36815 |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• delayed onset and reduced severity of arthritis: reduced immune cell infiltration, synovial hyperplasia and cartilage erosion
|
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• delayed onset and reduced severity of arthritis: reduced immune cell infiltration, synovial hyperplasia and cartilage erosion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mitral valve inflammation begins at 3 weeks of age and by 8 weeks, accumulation of inflammatory cells and interstitial thickening is obvious indicating fibroinflammatory mitral valve disease
• mononuclear phagocytes (macrophages and monocytes) constitute the vast majority of accumulated leukocytes
• frequency of TNF- and IL-6-producing phagocytes in inflamed mitral valve tissue is elevated, indicating an enrichment of cytokine-producing phagocytes within the inflamed mitral valves
• antibody blockade of either TNF or IL-6 beginning at the onset of mitral valve inflammation reduces mitral valve fibrosis and thickening
|
|
• rheumatoid arthritis occurs with disease onset transpiring between 25 and 35 days of age
(J:36815)
• arthritis occurrence is established by joint inspection and measure of ankle thickness, and histological confirmation in several mice
(J:36815)
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• mitral valve hydroxyproline content is elevated
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• by 8 weeks of age, mitral valves are fibrotic and thickened
• TNFR2 neutralization with a monoclonal antibody exacerbates mitral valve fibrosis and thickening
• blockade of either VLA-4 or VCAM-1 with monoclonal antibodies attenuates valve fibrosis and thickening
|
|
• mitral valve inflammation begins at 3 weeks of age and by 8 weeks, accumulation of inflammatory cells and interstitial thickening is obvious indicating fibroinflammatory mitral valve disease
• mononuclear phagocytes (macrophages and monocytes) constitute the vast majority of accumulated leukocytes
• frequency of TNF- and IL-6-producing phagocytes in inflamed mitral valve tissue is elevated, indicating an enrichment of cytokine-producing phagocytes within the inflamed mitral valves
• antibody blockade of either TNF or IL-6 beginning at the onset of mitral valve inflammation reduces mitral valve fibrosis and thickening
|
|
• mitral valve hydroxyproline content is elevated
|
|
• rheumatoid arthritis occurs with disease onset transpiring between 25 and 35 days of age
(J:36815)
• arthritis occurrence is established by joint inspection and measure of ankle thickness, and histological confirmation in several mice
(J:36815)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| mitral valve disease | DOID:61 | J:275827 | ||
| rheumatoid arthritis | DOID:7148 |
OMIM:180300 |
J:36815 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• macrophage cells make up a large number of cells found in inflamed joints
|
|
• splenomegaly is often observed
|
|
• clonal deletion is evident in the thymus of neonatal mice with reduced numbers of total cells and aberrant percentages of single-positive populations
• single-positive populations normalize by 4 weeks of age though total cell numbers are still reduced
• clonal deletion affects T cell populations in the periphery with a paucity of single-positive T cells in young mice and chronically reduced CD4+ population in adults
|
|
• spleen and lymph node B cell numbers are increased 1.75-fold in mice suffering from arthritis
|
|
• CD4+ T cells are virtually absent in the spleens of mice under 2 weeks of age
• CD4+ T cell numbers are reduced by 3.1-fold in the spleens of adult mice
|
|
• CD8 +T cells numbers are reduced in mice under 3 weeks of age
|
|
• neutrophils make up a large number of cells found in inflamed joints
|
|
• serum IgG1 levels are dramatically increased
|
|
• a greater proportion of T cells express late activation markers (CD44hi CD62Llo, CD45RBlo) than in transgene negative controls
|
|
• T cells expressing the transgenic TCR proliferate in response to antigen presenting cells expressing Class II MHC from a H2g7 locus in the absence of any antigen
|
|
• Background Sensitivity: transgenic T cells from mice on a NOD background have lower levels of T cell receptor expressed
• Background Sensitivity: transgenic T cells from mice on a NOD background have a severe reduction in response to its cognate antigen (RNAse peptide) presented by Ak than do transgenic T cells from a C57BL/6 background
• hybridomas created from these T cells respond normally to antigen suggesting a cell intrinsic anergy
|
|
• Background Sensitivity: transgenic mice crossed to a NOD background develop rheumatoid arthritis
• distal paws become red and swollen
• all transgenic mice have significantly swollen ankles by 30 days of age with the degree of swelling symmetrical on either limb
• as mice age hyperextension of the ankle, valgus deviation of the knee and hyperpronation of the toes occur
• arthritis occurs in almost all joints with the exception of hip joints
• arthritis starts as fibrinoid material and a few cells are found in the articular cavity; edema sets in under the synovial lining, accompanied by neovascularithezation and some infiltration of inflammatory cells
• after a few weeks, disease is marked by extensive synovitis, affecting all areas of the joint with massive infiltration of inflammatory cells and beginnings of fibrosis
• after several months, the inflammation recedes leaving massive fibrosis, very little cartilage, and irregular shaped bone
|
|
• occurs as part of arthritis disease process
|
|
• immunoglobulin deposits occur along the peritubular basal membranes in the cortex and medulla
|
|
• immunoglobulin deposits are detected in the glomeruli
|
|
• bones are eroded from arthritis with anarchic reconstruction occurring afterwards
|
|
• rheumatoid arthritis leads to hyperpronation of the toes
|
|
• bones are eroded from arthritis with anarchic reconstruction occurring afterwards
|
|
• Background Sensitivity: transgenic mice crossed to a NOD background develop rheumatoid arthritis
• distal paws become red and swollen
• all transgenic mice have significantly swollen ankles by 30 days of age with the degree of swelling symmetrical on either limb
• as mice age hyperextension of the ankle, valgus deviation of the knee and hyperpronation of the toes occur
• arthritis occurs in almost all joints with the exception of hip joints
• arthritis starts as fibrinoid material and a few cells are found in the articular cavity; edema sets in under the synovial lining, accompanied by neovascularithezation and some infiltration of inflammatory cells
• after a few weeks, disease is marked by extensive synovitis, affecting all areas of the joint with massive infiltration of inflammatory cells and beginnings of fibrosis
• after several months, the inflammation recedes leaving massive fibrosis, very little cartilage, and irregular shaped bone
|
|
• occurs as part of arthritis disease process
|
|
• bones are eroded from arthritis with anarchic reconstruction occurring afterwards
|
|
• bones are eroded from arthritis with anarchic reconstruction occurring afterwards
|
|
• intervertebral inflammation occurs sporadically in these mice
|
|
• mobility is compromised due to arthritis
|
|
• immunoglobulin deposits occur along the peritubular basal membranes in the cortex and medulla
|
|
• immunoglobulin deposits are detected in the glomeruli
|
|
• macrophage cells make up a large number of cells found in inflamed joints
|
|
• splenomegaly is often observed
|
|
• clonal deletion is evident in the thymus of neonatal mice with reduced numbers of total cells and aberrant percentages of single-positive populations
• single-positive populations normalize by 4 weeks of age though total cell numbers are still reduced
• clonal deletion affects T cell populations in the periphery with a paucity of single-positive T cells in young mice and chronically reduced CD4+ population in adults
|
|
• spleen and lymph node B cell numbers are increased 1.75-fold in mice suffering from arthritis
|
|
• CD4+ T cells are virtually absent in the spleens of mice under 2 weeks of age
• CD4+ T cell numbers are reduced by 3.1-fold in the spleens of adult mice
|
|
• CD8 +T cells numbers are reduced in mice under 3 weeks of age
|
|
• neutrophils make up a large number of cells found in inflamed joints
|
|
• serum IgG1 levels are dramatically increased
|
|
• a greater proportion of T cells express late activation markers (CD44hi CD62Llo, CD45RBlo) than in transgene negative controls
|
|
• T cells expressing the transgenic TCR proliferate in response to antigen presenting cells expressing Class II MHC from a H2g7 locus in the absence of any antigen
|
|
• macrophage cells make up a large number of cells found in inflamed joints
|
|
• T cells expressing the transgenic TCR proliferate in response to antigen presenting cells expressing Class II MHC from a H2g7 locus in the absence of any antigen
|
|
• splenomegaly is often observed
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| rheumatoid arthritis | DOID:7148 |
OMIM:180300 |
J:36815 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 05/07/2024 MGI 6.23 |
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