Selection of a mtDNA sequence variant in hepatocytes of heteroplasmic mice is not due to differences in respiratory chain function or efficiency of replication
Bibliographic record
Abstract
We have previously constructed lines of heteroplasmic mice from two inbred strains (NZB/BinJ and BALB/c) to investigate the mechanisms of segregation of mtDNA sequence variants. Analysis of the segregation behaviour of mtDNA in several tissues showed that the NZB genotype was invariably selected in liver/kidney and the BALB genotype in blood/spleen. Segregation was not significant in post-mitotic tissues. Here we have investigated this novel pattern of mtDNA segregation in isolated hepatocytes to determine the mechanism of selection. Polarographic measurements of respiratory chain function showed no difference between mitochondria containing either 0 or 91-97% NZB mtDNAs on a BALB nuclear background. Single-cell PCR analysis of mtDNA in isolated hepatocytes demonstrated that most hepatocytes eventually fix the NZB genotype. The rate of selection was constant with time and independent of the initial genotype frequency. Based on a mtDNA replication rate of 9.4 days, NZB mtDNA has an approximately 14% selective advantage over BALB mtDNA; however, in vivo pulse labelling with BrdU demonstrated that this was not based on efficiency of replication. Surprisingly, when hepatocytes were cultured in vitro, the majority of independent colonies selected BALB mtDNA, even if they were nearly fixed for the NZB mtDNA genotype when initially plated. These data suggest that selection for NZB mtDNA in the liver of these mice is not based on respiratory chain function at the cellular or organellar level, or a simple replicative advantage, but on a factor(s) involved with mtDNA maintenance.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".