Evidence for linkage of Type 1 Diabetes (T1D) resistance and upregulation of eotaxin (CCL11) in pancreatic beta cells to a chromosome 12 locus in the Biobreeding rat (49.2)
Bibliographic record
Abstract
Abstract The Biobreeding (BB) rat spontaneously develops autoimmune Type 1 Diabetes (T1D). We tested the hypothesis that the recently reported upregulation of CCL11 in BB rat βcells prior to insulitis is genetically determined and linked to T1D. This time-dependent upregulation of CCL11 transcription was not observed in T1D resistant ACI rats. Therefore linkage analysis for T1D and pancreatic CCL11 was performed in a conditioned cross/intercross between BB and ACI rats where all animals (n=574) carried T1D susceptibility alleles at the two known BB rat T1D genes. Eight T1D loci (chr 1, 2, 3, 2 in 6, 12, 14 and 17) were mapped establishing the polygenic nature of T1D in the BB rat and at three of these (chr 1, 3 and 12) the BB allele confers T1D resistance. Strikingly, upregulation of pancreatic CCL11 transcription mapped to the T1D locus on chromosome 12 (LOD=3.65) and the peak of linkage (D12rat51) was the same for the two traits. At D12rat51, homozygosity for the BB allele confers high levels of pancreatic eotaxin expression and T1D resistance, raising the possibility that upregulation of the Th2 chemokine CCL11 in the target tissue of the anti-pancreatic autoimmune process is protective. Research supported by Genome Canada and Banting and Best Diabetes Centre.
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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 | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".