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Hypoventilation in the Mdx Mouse Model of Duchenne Muscular Dystrophy
Author(s) -
Burns David P,
Arijit Roy,
McDonald Fiona,
Wilson Richard J,
O'Halloran Ken D
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb742
Subject(s) - duchenne muscular dystrophy , mdx mouse , dystrophin , medicine , endocrinology , ventilation (architecture) , respiratory minute volume , respiratory system , hypercapnia , muscular dystrophy , cardiology , mechanical engineering , engineering
Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by a lack of the structural protein dystrophin. Patients have severe muscle wasting and chronic respiratory insufficiency. Hypoventilation and sleep disordered breathing are both common features of the disease and are known to culminate in periods of hypoxaemia and hypercapnia. There is a paucity of information regarding the control of breathing in animal models of DMD. We measured ventilation, oxygen consumption (VO 2 ) and carbon dioxide (VCO 2 ) production in freely behaving mdx (dystrophin deficient; n=11) and wild‐type (WT; n=10) mice at 8 weeks of age. qRT‐PCR was used to examine inflammation and hypoxia associated gene expression in diaphragm muscle from WT and mdx mice. Minute ventilation (V E ; whole‐body plethysmography) was significantly reduced in mdx mice compared with WT controls (30% reduction). There was no significant difference in VO 2 and VCO 2 when expressed in absolute terms. Carotid sinus nerve unitary discharge was significantly depressed during normoxia in mdx (n=6) compared with WT (n=6) ex vivo perfused preparations. NF‐kB and TNF‐α mRNA expression were both significantly increased in mdx diaphragm compared with WT. HIF‐1α was significantly increased, while HIF‐2α was significantly decreased in mdx diaphragm muscle. Young mdx mice hypoventilate during air breathing (decreased V E /VCO 2 ), which likely relates to reduced carotid body discharge during normoxia. Mdx diaphragm muscle is in a pro‐inflammatory state and there is differential expression of hypoxia associated genes. We reveal that respiratory control is altered in the mdx mouse model of DMD at a young age. Support or Funding Information Funded by the Department of Physiology, School of Medicine, University College Cork and Muscular Dystrophy Ireland.