{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:23:30Z","timestamp":1790731410200,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T00:00:00Z","timestamp":1507507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000145","name":"Alberta Innovates - Health Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Respiratory failure is a leading cause of mortality in Duchenne muscular dystrophy (DMD), but little is known about the control of breathing in DMD and animal models.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that young (8\u00a0weeks of age) <jats:italic>mdx<\/jats:italic> mice hypoventilate during basal breathing due to reduced tidal volume. Basal CO<jats:sub>2<\/jats:sub> production is equivalent in wild\u2010type and <jats:italic>mdx<\/jats:italic> mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that carotid bodies from <jats:italic>mdx<\/jats:italic> mice have blunted responses to hyperoxia, revealing hypoactivity in normoxia. However, carotid body, ventilatory and metabolic responses to hypoxia are equivalent in wild\u2010type and <jats:italic>mdx<\/jats:italic> mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our study revealed profound muscle weakness and muscle fibre remodelling in young <jats:italic>mdx<\/jats:italic> diaphragm, suggesting severe mechanical disadvantage in <jats:italic>mdx<\/jats:italic> mice at an early age.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our novel finding of potentiated neural motor drive to breathe in <jats:italic>mdx<\/jats:italic> mice during maximal chemoactivation suggests compensatory neuroplasticity enhancing respiratory motor output to the diaphragm and probably other accessory muscles.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Patients with Duchenne muscular dystrophy (DMD) hypoventilate with consequential arterial blood gas derangement relevant to disease progression. Whereas deficits in DMD diaphragm are recognized, there is a paucity of knowledge in respect of the neural control of breathing in dystrophinopathies. We sought to perform an analysis of respiratory control in a model of DMD, the <jats:italic>mdx<\/jats:italic> mouse. In 8\u2010week\u2010old male wild\u2010type and <jats:italic>mdx<\/jats:italic> mice, ventilation and metabolism, carotid body afferent activity, diaphragm muscle force\u2010generating capacity, and muscle fibre size, distribution and centronucleation were determined. Diaphragm EMG activity and responsiveness to chemostimulation was determined. During normoxia, <jats:italic>mdx<\/jats:italic> mice hypoventilated, owing to a reduction in tidal volume. Basal CO<jats:sub>2<\/jats:sub> production was not different between wild\u2010type and <jats:italic>mdx<\/jats:italic> mice. Carotid sinus nerve responses to hyperoxia were blunted in <jats:italic>mdx<\/jats:italic>, suggesting hypoactivity. However, carotid body, ventilatory and metabolic responses to hypoxia were equivalent in wild\u2010type and <jats:italic>mdx<\/jats:italic> mice. Diaphragm force was severely depressed in <jats:italic>mdx<\/jats:italic> mice, with evidence of fibre remodelling and damage. Diaphragm EMG responses to chemoactivation were enhanced in <jats:italic>mdx<\/jats:italic> mice. We conclude that there is evidence of chronic hypoventilation in young <jats:italic>mdx<\/jats:italic> mice. Diaphragm dysfunction confers mechanical deficiency in <jats:italic>mdx<\/jats:italic> resulting in impaired capacity to generate normal tidal volume at rest and decreased absolute ventilation during chemoactivation. Enhanced <jats:italic>mdx<\/jats:italic> diaphragm EMG responsiveness suggests compensatory neuroplasticity facilitating respiratory motor output, which may extend to accessory muscles of breathing. Our results may have relevance to emerging treatments for human DMD aiming to preserve ventilatory capacity.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274792","type":"journal-article","created":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T00:53:10Z","timestamp":1506473590000},"page":"6653-6672","source":"Crossref","is-referenced-by-count":44,"title":["Sensorimotor control of breathing in the <i>mdx<\/i> mouse model of Duchenne muscular dystrophy"],"prefix":"10.1113","volume":"595","author":[{"given":"David P.","family":"Burns","sequence":"first","affiliation":[{"name":"Department of Physiology University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-9227","authenticated-orcid":false,"given":"Arijit","family":"Roy","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute University of Calgary  Calgary Alberta 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