Cardiac, respiratory, and physical activity profiles in young D2‐mdx dystrophic mice
Authors: Quindry John C. , Quindry Tiffany S. , Tiemessen Kathryn , Selsby Joshua T. 
Published: June 2021

Duchenne muscular dystrophy (DMD), caused by the absence of dystrophin protein, elicits pathological outcomes in cardiac and skeletal muscle. In DMD patients, physiologic declines include severe physical inactivity and cardiac and respiratory dysfunction. Our recent findings in a variety of murine models of DMD the fact that various dystrophic mouse strains exhibit variable outcomes in terms of spontaneous physical activity, cardiac function, and respiratory function, measured in vivo. Recent research emphases include the examination of clinically‐relevant outcomes, such as cardiac and respiratory function, in novel mouse strains that better recapitulate clinical pathology at cellular, tissue, and system levels. One such strain, the D2‐mdx (n=80) mouse, has only been examined in a few preliminary investigations. Thus, the purpose of this study was to characterize the extent to which D2‐mdx mice, and their healthy background strain (D2J, n=10), exhibit differences in spontaneous physical activity and cardiac and respiratory function at 4 months of age. To address this question, spontaneous physical activity was quantified at 40 time points for a mouse‐specific ethnogram. Cardiac function was examined via echocardiography and respiratory function by whole body plethysmography. Analyses of echocardiographic data indicate percent fractional shortening (D2J 43.0±14.7%, D2‐mdx 45.8±9.3%; p=0.132), ejection fraction (D2J 66.9±7.7%, D2‐mdx 68.6±7.711.1%; p=0.647), stroke volume (D2J 27.1±6.7ml, D2‐mdx 18.6±5.3ml; p=0.807), cardiac output (D2J 11.9±2.8 ml, D2‐mdx 7.8±2.5 ml; p=0.693), and left ventricular mass (D2J 133.8±21.2 mg, D2‐mdx 114.6±224.5 mg; p=0.435) were similar between groups. Respiratory variables including frequency (D2J 344±30 bpm, D2‐mdx 359±21 bpm; p=0.051), tidal volume (D2J 0.39±0.04 ml, D2‐mdx 0.38±0.04 ml; p=0.934), minute ventilation (D2J 135.3±11.7 ml/min, D2‐mdx 136.3±8.9 ml/min; p=0.392), and expiratory time (D2J 0.101±0.009 sec, D2‐mdx 0.096±0.006 sec; p=0.068) were similar between groups, while inspiratory time (D2J 0.079±0.007 sec, D2‐mdx 0.075±0.004 sec; p=0.024) was significantly different between strains. Spontaneous physical activity (counts) were similar for sitting (D2J 6.1±6.4, D2‐mdx 11.1±9.8; p=0.217), standing (D2J 25.8±7.8, D2‐mdx 21.9±8.9; p=0.297), eat/drink (D2J 11.9±8.4, D2‐mdx 11.5±7.7; p=0.497), socializing (D2J 14.6±3.7, D2‐mdx 12.9±5.9; p=0.115), walking (D2J 28.3±5.5, D2‐mdx 24.9±9.0; p=0.160), running (D2J 3.0±4.1, D2‐mdx 1.5±2.2; p=0.165), and jumping (D2J 3.3±3.2, D2‐mdx 2.4±3.3; p=0.853), while climbing (D2J 4.2±8.5, D2‐mdx 1.1±2.3; p<0.000) was decreased in the dystrophic strain. Findings suggest that at 4 months of age D2J and D2‐mdx mice exhibit similar cardiac function, respiratory function, and physical activity patterns, with only selected variables being different between strains. These differences, while limited, are consistent with dystrophinopathy.Support or Funding InformationParent Project Muscular Dystrophy & Ryan's Quest FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.