Selective disruption of acetylcholine synthesis in subsets of motor neurons: A new model of late-onset motor neuron disease

Marie José Lecomte, Chloé Bertolus, Julie Santamaria, Anne Laure Bauchet, Marc Herbin, Françoise Saurini, Hidemi Misawa, Thierry Maisonobe, Pierre François Pradat, Marika Nosten-Bertrand, Jacques Mallet, Sylvie Berrard

研究成果: Article査読

6 被引用数 (Scopus)


Motor neuron diseases are characterized by the selective chronic dysfunction of a subset of motor neurons and the subsequent impairment of neuromuscular function. To reproduce in the mouse these hallmarks of diseases affecting motor neurons, we generated a mouse line in which ~. 40% of motor neurons in the spinal cord and the brainstem become unable to sustain neuromuscular transmission. These mice were obtained by conditional knockout of the gene encoding choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine. The mutant mice are viable and spontaneously display abnormal phenotypes that worsen with age including hunched back, reduced lifespan, weight loss, as well as striking deficits in muscle strength and motor function. This slowly progressive neuromuscular dysfunction is accompanied by muscle fiber histopathological features characteristic of neurogenic diseases. Unexpectedly, most changes appeared with a 6-month delay relative to the onset of reduction in ChAT levels, suggesting that compensatory mechanisms preserve muscular function for several months and then are overwhelmed. Deterioration of mouse phenotype after ChAT gene disruption is a specific aging process reminiscent of human pathological situations, particularly among survivors of paralytic poliomyelitis. These mutant mice may represent an invaluable tool to determine the sequence of events that follow the loss of function of a motor neuron subset as the disease progresses, and to evaluate therapeutic strategies. They also offer the opportunity to explore fundamental issues of motor neuron biology.

ジャーナルNeurobiology of Disease
出版ステータスPublished - 2014 5月

ASJC Scopus subject areas

  • 神経学


「Selective disruption of acetylcholine synthesis in subsets of motor neurons: A new model of late-onset motor neuron disease」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。