Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
Bibliographic record
Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder. In 2007, a novel locus, SAX2, which is located on chromosome 17p13 and contains 3 genes, ankyrin repeat and FYVE domain-containing 1 (ANKFY1), β-arrestin 2 (ARRB2) and kinesin family member 1C (KIF1C), was linked to ARSACS. We generated Ankfy1 heterozygous (Ankfy1/+) mice to establish an animal model and examine the pathophysiological basis of ARSACS. The transgenic mice displayed an abnormal gait with progressive motor and cerebellar nerve dysfunction that was highly reminiscent of ARSACS. These clinical features were accompanied by an early-onset and progressive loss of Purkinje cells, followed by gliosis. Additionally, the loss of Ankfy1 function resulted in an abnormal expression of neurotrophic factors (NTFs) in the Ankfy1/+ mouse cerebellum. Moreover, Purkinje cells cultured from neonatal Ankfy1/+ mice exhibited a shorter dendritic length and decreased numbers of dendritic spines. Importantly, cerebellar Purkinje cells from Ankfy1/+ mice and cells transfected with a lentiviral Ankfy1 shRNA underwent apoptosis. We propose that transgenic Ankfy1/+ mice are a useful model for studying the pathogenesis of ARSACS and for exploring the molecular mechanisms involved in this neurodegenerative disease.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".