Résumé :
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INTRODUCTION : Myotonic dystrophy type 1 (DM1) is a genetic autosomal dominant multisystem disease resulting from an unstable CTG repeat expansion of DMPK gene on chromosome19q. Acute and chronic respiratory failure are frequent complications in patients with DM1, potentially life-threatening. The causes may be varied and the pathological mechanisms of the respiratory problems are still not completely known. Respiratory dysfunction may have a central origin with decreased respiratory drive, or peripheral origin such as weakness of the diaphragmatic muscles, or both. To study the mechanisms underlying respiratory failure, the use of a reliable DM1 animal model becomes essential. AIM : In this study we investigate whether the transgenic mice DMSXL carrying more than 1300 CTG and displaying severe DM1 phenotype have respiratory dysfunction. METHOD : Breathing function was assessed by using a pressure plethysmography (Respiromax, Columbus Instruments,USA). Under the same conditions, several parameters were measured in DMSXL and control mice. RESULTS : The analysis of respiratory parameters in awake mice revealed a significant decrease in tidal volume (0.208±0.055 ml vs 0.312±0.051) and in volume per minute (55.98±10.08 ml vs 85.15±13.31) in DMSXL mice when compared to controls taken from the same litter. We also measured the respiratory parameters in anaesthetized mice, which revealed that the respiratory rate (breaths/min) in DMSXL mice is significantly (P<0.01) decreased compared to controls (87.8±5.3 vs 125.7±14.4). Also the tidal volume was significantly (P<0.01) reduced in DMSXL mice (0.29±0.013 ml) compared to controls (0.38±0.041ml). Consequently, the mean value for minute volume/weight (Tidal volume X breathing frequency/weight) was also reduced in DMSXL mice compared to controls (0.94±0.09 vs1.40±0.17). Since DMSXL mice are smaller (22±2.0 g) than control mice (33.8±3.6 g), we measured the respiratory function in control mice that have similar size and weight (24±0.6 g) as the DMSXL mice. The results of these experiments confirmed that the changes in respiratory pattern observed in DMSXL transgenic mice are not related to the size of the animal. CONCLUSION : Our results provide evidence of impaired respiratory function in DMSXL mice. (Supported by AFM).
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