Overexpression of human decoy receptor 3 in mice results in a systemic lupus erythematosus–like syndrome
Bibliographic record
Abstract
OBJECTIVE: Decoy receptor 3 (DcR3), a tumor necrosis factor receptor family member, is a secreted protein that can enhance cell survival by interfering with multiple apoptosis pathways. This study was undertaken to investigate the role of DcR3 in the pathogenesis of autoimmune disease. METHODS: We generated transgenic mice with actin promoter-driven expression of human DcR3 and investigated the development of autoimmune disease in these mice. RESULTS: T cell immune responses were compromised in young DcR3-transgenic mice. Beyond 5-6 months of age, transgenic mice developed a systemic lupus erythematosus (SLE)-like syndrome, with numerous features of the disease. They produced autoantibodies against double-stranded DNA. Their kidneys showed pathologic changes indicative of glomerular nephritis and IgG and C3 deposition, and proteinuria, leukocyturia, and hematuria, were evident. Aged transgenic mice also developed skin lesions and lymphocyte infiltration in the liver, and exhibited leukopenia, anemia, and thrombocytopenia. The SLE-like syndrome penetrance in DcR3-transgenic mice was sex associated, occurring in approximately 60% of females versus 20% of males. Exogenous recombinant DcR3 or endogenous DcR3 produced by transgenic T cells effectively protected T cells against activation-induced apoptosis in vitro. Probably as a consequence of this, CD4 cells with a phenotype of previous activation were increased in the peripheral blood of transgenic mice beyond 6 months of age. CONCLUSION: These results show that DcR3 overexpression could lead to an SLE-like syndrome in mice.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".