The haemochromatosis protein HFE induces an apparent iron-deficient phenotype in H1299 cells that is not corrected by co-expression of beta2-microglobulin
Bibliographic record
Abstract
HFE, an atypical MHC class I type molecule, has a critical, yet still elusive function in the regulation of systemic iron metabolism. HFE mutations are linked to hereditary haemochromatosis type 1, a common autosomal recessive disorder of iron overload. Most patients are homozygous for a C282Y point mutation that abrogates the interaction of HFE with beta(2)-microglobulin (beta(2)M) and, thus, impairs its proper processing and expression on the cell surface. An H63D substitution is also associated with disease. To investigate the function of HFE we have generated clones of human H1299 lung cancer cells that express wild-type, C282Y or H63D HFE under the control of a tetracycline-inducible promoter. Consistent with earlier observations in other cell lines, the expression of wild-type or H63D, but not C282Y, HFE induces an apparent iron-deficient phenotype, manifested in the activation of iron-regulatory protein and concomitant increase in transferrin receptor levels and decrease in ferritin content. This phenotype persists in cells expressing wild-type HFE after transfection with a beta(2)M cDNA. Whereas endogenous beta(2)M is sufficient for the presentation of at least a fraction of chimeric HFE on the cell surface, this effect is stimulated by approx. 2.8-fold in beta(2)M transfectants. The co-expression of exogenous beta(2)M does not significantly affect the half-life of HFE. These results suggest that the apparent iron-deficient phenotype elicited by HFE is not linked to beta(2)M insufficiency.
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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 | 0.001 |
| 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".