Human Genetics

, Volume 113, Issue 4, pp 297–306 | Cite as

The cnm locus, a canine homologue of human autosomal forms of centronuclear myopathy, maps to chromosome 2

  • Laurent Tiret
  • Stéphane Blot
  • Jean-Louis Kessler
  • Hugues Gaillot
  • Matthew Breen
  • Jean-Jacques Panthier
Original Investigation


Myotubular/centronuclear myopathies are a nosological group of hereditary disorders characterised by severe architectural and metabolic remodelling of skeletal muscle fibres. In most myofibres, nuclei are found at an abnormal central position within a halo devoid of myofibrillar proteins. The X-linked form (myotubular myopathy) is the most prevalent and severe form in human, leading to death during early postnatal life. Maturation of fibres is not completed and fibres resemble myotubes. Linkage analysis in human has helped to identify MTM1 as the morbid gene. MTM1 encodes myotubularin, a dual protein phosphatase. In families in which myotubular myopathy segregates, detected mutations in MTM1 abolish the specific phosphatase activity targeting the second messenger phosphatidylinositol 3-phosphate. Autosomal forms (centronuclear) have a later onset and are often compatible with life. At birth, fibres are normally constituted but progressively follow remodelling with a secondary centralisation of nuclei. Their prevalence is low; hence, no linkage data can be performed and no molecular aetiology is known. In the Labrador Retriever, a spontaneous disorder strikingly mimics the clinical evolution of the human centronuclear myopathy. We have established a canine pedigree and show that the disorder segregates as an autosomal recessive trait in that pedigree. We have further mapped the dog locus to a region on chromosome 2 that is orthologous to human chromosome 10p. To date, no human MTM1 gene member has been mapped to this genetic region. This report thus describes the first spontaneous mammalian model of centronuclear myopathy and defines a new locus for this group of diseases.


Bacterial Artificial Chromosome Myopathy Bacterial Artificial Chromosome Clone Biceps Femoris Radiation Hybrid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Fanny Pilot, Nelly Da Silva and all the personnel from UMR 955, and Sandrine Vandormael-Pournin, Dominique Simon and Stéphanie Le Bras from the Institut Pasteur for their assistance in molecular techniques. We are grateful to Christophe Degueurce from UMR INRA-ENVA of Biomécanique et Pathologie Locomotrice du Cheval for expert advice in biomechanics and anatomy, Dr. Jean-Laurent Thibaud for medical expertise, and Sophie Angleviel, Ingrid Gruyer, Andrea Mortier, Stéphanie Lemevel and Willy Deshayes for taking care of the animals. We are indebted to Geneviève Aubin-Houzelstein and Dina Chaya-Moghrabi for their reading and improvement of the manuscript. We acknowledge the Association Française contre les Myopathies (AFM) and Royal Canin for their financial support. This work also received financial support from the Association pour la Recherche sur le Cancer (ARC, grant 99/7469). M. Breen is supported by funds from the American Kennel Club Canine Health Foundation and the Pet Plan Charitable Trust.


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Laurent Tiret
    • 1
  • Stéphane Blot
    • 2
  • Jean-Louis Kessler
    • 1
  • Hugues Gaillot
    • 1
  • Matthew Breen
    • 3
  • Jean-Jacques Panthier
    • 1
  1. 1.UMR 955 INRA-ENVA de Génétique Moléculaire et CellulaireEcole Nationale Vétérinaire d'AlfortMaisons-AlfortFrance
  2. 2.Laboratoire de NeurobiologieEcole Nationale Vétérinaire d'AlfortMaisons-AlfortFrance
  3. 3.Department of Molecular Biomedical Sciences, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA

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