title: Plasminogen activators in the neuromuscular system of the wobbler mutant mouse.
abstract: Wobbler, the neurological mutant mouse, carries an autosomal recessive gene (wr) and has been characterized as a model of lower motoneuron disorders with associated muscle atrophy, denervation and reinnervation. During normal murine neuromuscular development a decrease in muscle plasminogen activator (PA) activity accompanies synapse maturation. In contrast, experimental denervation in adult mice leads to an increase in muscle PA activity. The purpose of the present study was to determine the possible involvement of PAs in the denervation/reinnervation phenomena and motoneuron degeneration that characterize the wobbler mutant mouse. We determined the degree of innervation and its characteristics in wobbler mice by measuring choline acetyltransferase (ChAT) activity. We measured ChAT in the spinal cord as well as in two different muscles known to be differentially affected, biceps brachii and gastrocnemius. We found a sharp decrease of ChAT activity in both muscles but not in spinal cord extracts. We estimated the extent of sprouting by the silver/cholinesterase stain. Motoneuron terminal sprouting, not detected in normal animals, was present in 40% of the neuromuscular junctions in wobbler mice. We estimated specific PA activities in biceps brachii and gastrocnemius muscle extracts, as well as spinal cord extracts, using both an amidolytic assay and fibrin zymography. Increased PA, predominantly urokinase-PA (uPA), was observed in wobbler mouse muscle. A greater uPA was detected in biceps brachii muscle than in gastrocnemius muscle, which is less impaired by the mutation. There was no change in spinal cord PA, although tissue type PA (tPA) is the predominant PA type there.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: INSERM U. 153, CNRS URA 614, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Blondet
authors.forename: G
authors.initials: G
authors.lastname: Barlovatz-Meimon
authors.forename: B W
authors.initials: BW
authors.lastname: Festoff
authors.forename: C
authors.initials: C
authors.lastname: Soria
authors.forename: J
authors.initials: J
authors.lastname: Soria
authors.forename: F
authors.initials: F
authors.lastname: Rieger
authors.forename: D
authors.initials: D
authors.lastname: Hantai
mesh_terms: D000577:Amides / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008970:Molecular Weight; D009046:Motor Neurons / Q000201:enzymology; D009124:Muscle Proteins / Q000032:analysis; D009132:Muscles / Q000201:enzymology*; D009411:Nerve Endings / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009468:Neuromuscular Diseases / Q000378:metabolism*; D013116:Spinal Cord / Q000201:enzymology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D000577:Amides; D015415:Biomarkers; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D002795:Choline O-Acetyltransferase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator