Congenic Mapping of the Diabetogenic Locus<i>Idd4</i>to a 5.2-cM Region of Chromosome 11 in NOD Mice
Bibliographic record
Abstract
Twenty diabetes susceptibility loci on 12 mouse chromosomes have been identified to control the development of type 1 diabetes at the level of either initiation of insulitis or progression from insulitis to overt diabetes or both. Previously, we demonstrated that the genetic control of T-cell proliferative unresponsiveness in nonobese diabetic (NOD) mice is linked to Idd4 on mouse chromosome 11. Here, we show by congenic mapping of three newly generated NOD.B6Idd4 diabetes-resistant mouse strains that Idd4 is limited to a 5.2-cM interval of chromosome 11. This B6-derived region expressed in NOD.B6Idd4A mice maps between the D11Nds1 (43.8 cM) and D11Mit38/D11Mit325 (49.0 cM) markers and dramatically reduces the development of both insulitis and type 1 diabetes. NOD.B6Idd4B and NOD.B6Idd4C mice, which carry a smaller B6-derived segment of chromosome 11 that spans <5.2 cM distal to D11Nds1, exhibit protection against type 1 diabetes with the restoration of T-cell proliferation. Our findings suggest that diabetes resistance conferred by Idd4 may be mediated by the Idd4.1 and Idd4.2 subloci. Idd4.1 is localized in the D11Nds1 interval that influences both diabetes and insulitis. Idd4.2 is localized within the D11Mit38/325 interval that mainly influences diabetes incidence and restores T-cell proliferative responsiveness. Three potential candidate genes, platelet activating factor acetylhydrolase Ib1, nitric oxide synthase-2, and CC chemokine genes, are localized in the 5.2-cM interval.
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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 | 0.000 |
| 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".