title: Failure of lower motor neuron radial outgrowth precedes retrograde degeneration in a feline model of spinal muscular atrophy.
abstract: Feline spinal muscular atrophy (SMA) is a fully penetrant, autosomal recessive lower motor neuron disease in domestic cats that clinically resembles human SMA Type III. A whole genome linkage scan identified a ∼140-kb deletion that abrogates expression of LIX1, a novel SMA candidate gene of unknown function. To characterize the progression of feline SMA, we assessed pathological changes in muscle and spinal cord from 3 days of age to beyond onset of clinical signs. Electromyographic (EMG) analysis indicating denervation occurred between 10 and 12 weeks, with the first neurological signs occurring at the same time. Compound motor action potential (CMAP) amplitudes were significantly reduced in the soleus and extensor carpi radialis muscles at 8-11 weeks. Quadriceps femoris muscle fibers from affected cats appeared smaller at 10 weeks; by 12 weeks atrophic fibers were more prevalent than in age-matched controls. In affected cats, significant loss of L5 ventral root axons was observed at 12 weeks. By 21 weeks of age, affected cats had 40% fewer L5 motor axons than normal. There was no significant difference in total L5 soma number, even at 21 weeks; thus degeneration begins distal to the cell body and proceeds retrogradely. Morphometric analysis of L5 ventral roots and horns revealed that 4 weeks prior to axon loss, motor axons in affected cats failed to undergo radial enlargement, suggesting a role for the putative disease gene LIX1 in radial growth of axons.
authors: Genetics Program, Michigan State University East Lansing, Michigan 48824, USA. wakelin1@msu.edu
authors: Erin N
authors: EN
authors: Wakeling
authors: Béatrice
authors: B
authors: Joussemet
authors: Patrick
authors: P
authors: Costiou
authors: Dominique
authors: D
authors: Fanuel
authors: Philippe
authors: P
authors: Moullier
authors: Martine
authors: M
authors: Barkats
authors: John C
authors: JC
authors: Fyfe
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002415:Cats; D049108:Cell Enlargement; D004195:Disease Models, Animal; D018450:Disease Progression; D004576:Electromyography; D008161:Lumbosacral Region; D018613:Microscopy, Confocal; D009046:Motor Neurons / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000473:pathology* / Q000503:physiopathology*; D016601:RNA-Binding Proteins / Q000235:genetics; D012183:Retrograde Degeneration / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D016601:RNA-Binding Proteins