title: Morphological analysis of neuromuscular junction development and degeneration in rodent lumbrical muscles.
abstract: BACKGROUND
  The neuromuscular junction (NMJ) is a specialised synapse formed between a lower motor neuron and a skeletal muscle fibre, and is an early pathological target in numerous nervous system disorders, including amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), and spinal muscular atrophy (SMA). Being able to accurately visualise and quantitatively characterise the NMJ in rodent models of neurological conditions, particularly during the early stages of disease, is thus of clear importance.
  
  
  METHODS
  We present a method for dissection of rodent deep lumbrical muscles located in the hind-paw, and describe how to perform immunofluorescent morphological analysis of their NMJs.
  
  
  RESULTS
  These techniques allow the temporal assessment of a number of developmental and pathological NMJ phenotypes in lumbrical muscles.
  
  
  METHODS
  Small muscles, such as the distal hind-limb lumbrical muscles, possess a major advantage over larger muscles, such as gastrocnemius, in that they can be whole-mounted and the entire innervation pattern visualised. This reduces preparation time and ambiguity when evaluating important neuromuscular phenotypes.
  
  
  CONCLUSIONS
  Together, these methods will allow the reader to perform a detailed and accurate analysis of the neuromuscular system in rodent models of disease in order to identify pertinent features of neuropathology.
authors: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
authors: James N
authors: JN
authors: Sleigh
authors: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors: Robert W
authors: RW
authors: Burgess
authors: Centre for Integrative Physiology & Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH8 9XD, UK.
authors: Thomas H
authors: TH
authors: Gillingwater
authors: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK. Electronic address: zameel.cader@ndcn.ox.ac.uk.
authors: M Zameel
authors: MZ
authors: Cader
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002038:Bungarotoxins / Q000378:metabolism; D004195:Disease Models, Animal; D006032:Glycine-tRNA Ligase / Q000235:genetics; D066298:In Vitro Techniques; D008161:Lumbosacral Region; D008562:Membrane Glycoproteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009121:Muscle Denervation / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000473:pathology*; D020511:Neuromuscular Junction Diseases / Q000235:genetics / Q000473:pathology*; D061848:Optical Imaging; D051381:Rats
chemical_list: D002038:Bungarotoxins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C489614:Sv2a protein, mouse; D006032:Glycine-tRNA Ligase
keywords: Lower motor neuron; Lumbrical muscle; Neurodegeneration; Neurodevelopment; Neuromuscular disease; Neuromuscular junction (NMJ)