Histopathology and Mitochondrial Function in Liver‐Specific LRPPRC Knockout Mice
Bibliographic record
Abstract
The French‐Canadian variant of Leigh Syndrome (LSFC) is an inherited mitochondrial respiratory chain disorder prevalent in the Saguenay‐Lac‐St‐Jean region of Quebec. It is caused by LRPPRC mutation, a leucine‐rich pentatricopeptide repeat protein that regulates the stability of mitochondrial mRNAs encoding proteins involved in oxidative phosphorylation. Mutated LRPPRC, present at low levels in all tissues from patients, causes a severe decrease in cytochrome c oxidase (COX) activity primarily in the brain and liver, leading to unpredictable subacute crises of neurodegeneration and hepatic lactic acidosis, killing 80% of children. To gain better knowledge of the disease, we characterized phenotype and mitochondrial function of mice harbouring liver‐specific inactivation of Lrpprc ( Lrpprc ‐HKO). Lrpprc ‐HKO mice are viable but display a general growth delay. Livers from 5 week‐old mice present loss of lobular organization, steatosis, cholestasis, necrosis/regeneration and severe reduction in COX/SDH staining ratio. Mitochondrial preparations present several functional abnormalities including: i) increased state 2 and lower state 3 respiration with substrates feeding complex I, II and IV, ii) lower capacity to oxidize fatty acids, iii) reduced H 2 O 2 release and scavenging and iv) increased resistance to Ca 2+ ‐induced PTP opening. These changes are associated with two primary molecular defects, which contribute to explain the phenotype: i) a severe loss of COX activity and ii) an ATPsynthase assembly defect. Studies are underway to mechanistically link these molecular defects with the observed mitochondrial dysfunction and identify further consequences of Lrpprc liver deletion.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".