Elucidating mother to offspring transmission of chronic wasting disease using a transgenic mouse model
Bibliographic record
Abstract
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE), or prion disease, of free-ranging and farmed cervids (deer, elk and moose). CWD is the only TSE in a wildlife population, which was initially discovered in a captive mule deer herd in a study shared between Colorado State University and University of Wyoming in 1967. CWD is the most readily transmitted of all the prion diseases and since its discovery has been identified in cervid populations in 24 states, 2 Canadian provinces, and the Republic of Korea. Horizontal transmission of prion diseases is thought to account for its exceptional transmission efficiency [2-10]. Recent studies published by our group provide evidence that transmission from mother to offspring may also be a contributing factor. In the work of this thesis, we employed a transgenic mouse system that expresses the cervid prion protein Tg(CerPrP-E226) to help elucidate the role of mother to offspring CWD transmission via hemochorial placentation. Females were inoculated with known CWD-positive material and subsequently bred with CWD-naïve males at various timepoints post inoculation to investigate if maternal/vertical transmission occurs in this host, as well as to further understand how this might occur. We examined the likelihood of prion trafficking in utero by analysis of mother: offspring pairs at different timepoints in CWD-infection and gestation, in addition to looking for infectious prions in milk collected from CWD-positive dams. We have demonstrated that CWD-infected Tg(CerPrP-E226) females successfully breed and bear offspring irrespective to TSE disease stage. Offspring born to CWD- infected females did not exhibit signs of TSE disease and lacked detectible PrPres via conventional methodologies. Interestingly, conversion competent prions were identified in the brains and spleens of offspring by highly sensitive amyloid seeding assays. The lack of symptoms in these offspring indicates covert prion transmission from mother to offspring, resulting in a potential silent-carrier status. As for our studies to further the understanding of the mechanisms behind this transmission, we identified CWD-prions in reproductive and mammary tissue, and spleen of Tg(CerPrP-E226) mouse mothers as early as 72 days post inoculation. In addition, we found minute quantities of amyloid conversion material in placenta and fetal tissues from mother:offspring pairs at varying timepoints in CWD-infection. We were unable to detect prions in milk collected from CWD-positive transgenic dams, leading us to hypothesize that the route of TSE transmission to offspring is likely a combination of environmental exposure, and/or very low concentrations of prions breaching the feto-maternal interface.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".