Mice Lacking α-Tubulin Acetyltransferase 1 Are Viable but Display α-Tubulin Acetylation Deficiency and Dentate Gyrus Distortion
Bibliographic record
Abstract
Background: Biological functions of mammalian Atat1 and its contribution to ␣-tubulin acetylation in vivo remain elusive.Results: Atat1-null mice are viable but possess deficient ␣-tubulin acetylation and a bulge in the dentate gyrus.Conclusion: Mouse Atat1 is a predominant ␣-tubulin acetyltransferase in vivo and fine-tunes hippocampus development.Significance: Mammalian Atat1 is not required for survival and development but may regulate more advanced functions.␣-Tubulin acetylation at Lys-40, located on the luminal side of microtubules, has been widely studied and used as a marker for stable microtubules in the cilia and other subcellular structures, but the functional consequences remain perplexing. Recent studies have shown that Mec-17 and its paralog are responsible for ␣-tubulin acetylation in Caenorhabditis elegans.There is one such protein known as Atat1 (␣-tubulin acetyltransferase 1) per higher organism.Zebrafish Atat1 appears to govern embryo development, raising the intriguing possibility that Atat1 is also critical for development in mammals.In addition to Atat1, three other mammalian acetyltransferases, ARD1-NAT1, ELP3, and GCN5, have been shown to acetylate ␣-tubulin in vitro, so an important question is how these four enzymes contribute to the acetylation in vivo.We demonstrate here that Atat1 is a major ␣-tubulin acetyltransferase in mice.It is widely expressed in mouse embryos and tissues.Although Atat1-null animals display no overt phenotypes, ␣-tubulin acetylation is lost in sperm flagella and the dentate gyrus is slightly deformed.Furthermore, human ATAT1 colocalizes on bundled microtubules with doublecortin.These results thus suggest that mouse Atat1 may regulate advanced functions such as learning and memory, thereby shedding novel light on the physiological roles of ␣-tubulin acetylation in mammals.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".