Variants in <i>Lrrk2</i> and <i>Snca</i> deficiency do not alter the course of primary encephalitis due to neurotropic reovirus T3D in newborn mice
Bibliographic record
Abstract
Abstract Variants of the leucine-rich repeat kinase-2 ( LRRK2 ) and α-synuclein ( SNCA ) genes are associated with Parkinson’s disease risk. We previously demonstrated that two Lrrk2 knock-in variants as well as Snca expression alter survival rates from combined pneumonitis and encephalitis following intranasal inoculation of newborn mice with a double-stranded RNA virus: respiratory-enteric-orphan virus, serotype-3 strain Dearing (reovirus T3D). Here, we examined whether outcomes of direct inoculation of the brain by reovirus T3D, which invariably causes lethal encephalitis within 15 days, would also be modified by variants in Lrrk2 and Snca . When we inoculated newborn mice intracerebrally with 5×10 2 plaque-forming units of reovirus T3D, we found that, when compared to wild-type littermates, Lrrk2 p.G2019S mutant mice and kinase-dead p.D1994S mutant animals showed the same time-to-death intervals post-infection, revealed no sex difference, and had similar viral titres in the brain. Furthermore, the reduction or absence of endogenous α-synuclein also did not alter the course of encephalitis in parallel studies. These outcomes are in contrast to those following the intranasal inoculation paradigm of newborn mice, in which Lrrk2 and wild-type α-synuclein were both protective in infection outcomes. Together, these findings suggest that the Parkinson’s disease-linked Lrrk2 and Snca genes contribute predominantly to systemic, innate responses by the host following reovirus T3D exposure.
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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 | 0.000 | 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 | 0.001 |
| 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".