title: Mild muscular features in tenascin-X knockout mice, a model of Ehlers-danlos syndrome.
abstract: BACKGROUND
  Tenascin-X (TNX) is an extracellular matrix (ECM) glycoprotein, the absence of which in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. A mouse model of TNX-deficient type EDS has been used to characterize the dermatological, orthopedic, and obstetrical features. The growing insight in the clinical overlap between myopathies and inherited connective tissue disorders asks for a study of the muscular characteristics of inherited connective tissue diseases. Therefore, this study aims to define the muscular phenotype of TNX knockout (KO) mice.
  
  
  METHODS
  We performed a comprehensive study on the muscular phenotype of these TNX KO mice, consisting of standardized clinical assessment, muscle histology, and gene expression profiling of muscle tissue. Furthermore, peripheral nerve composition was studied by histology and electron microscopy.
  
  
  RESULTS
  The main findings are the presence of mild muscle weakness, mild myopathic features on histology, and functional upregulation of genes encoding proteins involved in ECM degradation and synthesis. Additionally, sciatic nerve samples showed mildly reduced collagen fibril density of endoneurium.
  
  
  CONCLUSIONS
  The muscular phenotype of TNX KO mice consists of mild muscle weakness with histological signs of myopathy and of increased turnover of the ECM in muscle. Furthermore, mildly reduced diameter of myelinated fibers and reduction of collagen fibril density of endoneurium may correspond with polyneuropathy in TNX-deficient EDS patients. This comprehensive assessment can serve as a starting point for further investigations on neuromuscular function in TNX KO mice.
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, the Netherlands. n.voermans@neuro.umcn.nl
authors.forename: N C
authors.initials: NC
authors.lastname: Voermans
authors.forename: K
authors.initials: K
authors.lastname: Verrijp
authors.forename: L
authors.initials: L
authors.lastname: Eshuis
authors.forename: M C M
authors.initials: MC
authors.lastname: Balemans
authors.forename: D
authors.initials: D
authors.lastname: Egging
authors.forename: E
authors.initials: E
authors.lastname: Sterrenburg
authors.forename: I A L M
authors.initials: IA
authors.lastname: van Rooij
authors.forename: J A W M
authors.initials: JA
authors.lastname: van der Laak
authors.forename: J
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: S M
authors.initials: SM
authors.lastname: van der Maarel
authors.forename: M
authors.initials: M
authors.lastname: Lammens
authors.forename: B G
authors.initials: BG
authors.lastname: van Engelen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004535:Ehlers-Danlos Syndrome / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000503:physiopathology; D009132:Muscles / Q000473:pathology* / Q000503:physiopathology; D012584:Sciatic Nerve / Q000473:pathology; D019063:Tenascin / Q000172:deficiency*
chemical_list: D019063:Tenascin; C081865:tenascin X