MBNL loss of function in the motor unit alters neuromuscular communication

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Frison-Roche, Charles | Cottin, Steve | Lainé, Jeanne | Arandel, Ludovic | Halliez, Marius | Messéant, Julien | Lornage, Xavière | Swanson, Maurice, S | Furling, Denis | Rau, Fredérique

Edité par CCSD -

International audience. "DM1 pathophysiology have been studied through skeletal muscle, heart and brain but knowledge about spinal motor neurons (MN) involvement is limited. MN innervate skeletal muscle through neuromuscular junctions (NMJ) and prior reports identified RNA foci colocalizing with MBNL1 in DM1 MN and NMJ1, which display ultrastructural2 and possible functional abnormalities. To assess and dissect the role of MBNL in neuromuscular communication, we crossed mice invalidated ubiquitously for Mbnl1 (Mbnl1-KO) with mice deprived of Mbnl2 specifically in MN to obtain MN-dKO mice.Young MN-dKO mice show no NMJ or locomotion alterations. However after a couple of months, these mice progressively develop locomotion deficiencies that are associated with NMJ structural and ultrastructural defects, when compared to Mbnl1-KO mice. MBNL compound loss-of-function in MN significantly affects motor capacities and NMJ structure. Deficiency in NMJ maintenance, rather than development, may be responsible for NMJ abnormalities caused by MBNL loss. Identification of molecular alterations in MN of this mouse model as well as MBNL RNA targets in MN is ongoing. Altogether our work will help for a better knowledge of DM1 physiopathology."

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