Why the study?
Mouse models of mild spinal muscular atrophy have been challenging to generate, limiting understanding of pathophysiological events in milder disease forms and SMN depletion during aging.
Key points are not available for this paper at this time.
Population
Mouse model of mild spinal muscular atrophy
Design
Preclinical animal model study
New mild SMA mouse model enables aging and extra-neuronal studies; leaves open clinical translation pending human validation.
BACKGROUND: Mouse models of mild spinal muscular atrophy (SMA) have been extremely challenging to generate. This paucity of model systems has limited our understanding of pathophysiological events in milder forms of the disease and of the effect of SMN depletion during aging. METHODS: mice. This new model was characterized using behavioral testing, histology, western blot, muscle-nerve electrophysiology as well as ultrasonography to study classical SMA features and extra-neuronal involvement. FINDINGS: mice have normal survival, mild but sustained motor weakness, denervation and neuronal/neuromuscular junction (NMJ) transmission defects, and neurogenic muscle atrophy that are more prominent in male mice. Increased centrally located nuclei, intrinsic contractile and relaxation muscle defects were also identified in both female and male mice, with some male predominance. There was an absence of extra-neuronal pathology. INTERPRETATION: mouse provides a model of mild SMA, displaying some hallmark features including reduced weight, sustained motor weakness, electrophysiological transmission deficit, NMJ defects, and muscle atrophy. Early and prominent increase central nucleation and intrinsic electrophysiological deficits demonstrate the potential role played by muscle in SMA disease. The use of this model will allow for the understanding of the most susceptible pathogenic molecular changes in motor neurons and muscles, investigation of the effects of SMN depletion in aging, sex differences and most importantly will provide guidance for the currently aging SMA patients treated with the recently approved genetic therapies. FUNDING: This work was supported by Cure SMA/Families of SMA Canada (grant numbers KOT-1819 and KOT-2021); Muscular Dystrophy Association (USA) (grant number 575466); and Canadian Institutes of Health Research (CIHR) (grant number PJT-156379).
No takes yet. Share an insight, caveat, or question.
Deguise et al. (2020) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: