Investigating the effects of thermoneutral housing on skeletal and cardiac muscle function in D2 mdx mice
Bibliographic record
Abstract
Since its discovery, the mdx mouse has been the foundation for research on Duchenne muscular dystrophy (DMD) and its potential therapies. Although, nearly all studies using mdx mice as an experimental model have been conducted under “standard” lab conditions using room (22C) instead of thermoneutral (TN, 30C) temperature housing. Room temperature (RT) is a mild cold stress to mice, causing metabolic adaptations that can confound experimental results, limiting their interpretation and translation to humans. This study investigated the effects of housing temperature on whole-body metabolism and skeletal and cardiac muscle function in the mdx mouse. To this end, 20 D2 mdx mice (age 5 weeks, n = 10 per group) were housed at RT and TN for 10 weeks. Metabolic cage analysis demonstrated that TN housed mdx mice displayed significantly decreased VO2 consumption and reduced food intake that was likely due to lowered daily energy expenditure. TN housed mice also had significantly lower respiratory exchange ratio values, indicative of increased fat metabolism. However, there were no differences in body mass or composition (i.e., % lean and fat mass). Treadmill-to-fatigue experiments revealed no differences in exercise performance. Furthermore, ex vivo muscle contractility analysis displayed no differences in extensor digitorum longus or soleus specific force generation between TN and RT housed mice. Analysis of cardiac structure/function demonstrated that TN housed mdx mice exhibited a reduction in cardiac output, which we attributed to diastolic dysfunction. While ejection fraction and fractional shortening were not different among the two groups, TN housing led to a significant reduction in end diastolic volume (EDV) and left ventricle internal diameter (diastole, LVID;d), as well as increased relative wall thickness (diastole, RWT;d) compared to RT housed mice. Though isovolumic relaxation time was prolonged in TN-housed mice, this did not reach statistical significance. Taken together, our results demonstrate that TN housing had minimal effects on skeletal muscle contractility, but did lead to signs of diastolic dysfunction in young mdx mice. Future studies will examine the effects of TN housing in aged mdx mice, when systolic dysfunction occurs, as well as any influence of TN housing on the efficacy of potential muscle wasting therapeutics. Overall, our results support the growing literature that highlights the importance of selecting the appropriate housing temperature when studying metabolism or muscle wasting conditions in mice. NSERC This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".