Comparison of Huntington’s disease phenotype progression in male and female heterozygous FDNQ175 mice
Bibliographic record
Abstract
Huntington's Disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment due to the expansion of a polyglutamine (CAG) repeat in the N-terminal region of the huntingtin (Htt) protein. The creation of HD mouse models represents a critical step in the research for HD treatment. Among the currently available HD mouse models, the zQ175 knock-in mouse line is the first to display robust disease phenotype on a heterozygous background. The newer FDNQ175 mouse model is derived from the zQ175 mouse line and presents a more aggressive phenotype. Moreover, increasing evidence has implicated sex as a contributing factor in the progression of HD symptoms. Here, we compared the progression of HD phenotypes in male and female heterozygous FDNQ175 mice. We found that both male and female heterozygous mice showed deficits in forelimb grip strength and cognition as early as 6 months of age. However, female FDNQ175 mice were less vulnerable to HD-associated decline in limb coordination and movement. Neither male nor female FDNQ175 mice exhibited reduced locomotor activity in the open field or exhibit consistent differences in anxiety at 6-12 months of age. Both male and female FDNQ175 mice exhibited increased numbers of huntingtin aggregates with age and 8-month-old female FDNQ175 mice had significantly more aggregates than their male counterparts. Taken together, our results provide further evidence that sex can influence the progression of HD phenotype in preclinical animal models and must be taken into consideration for future HD research.
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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 | 0.001 |
| 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".