Muscle degeneration in neuraminidase 1-deficient mice results from infiltration of the muscle fibers by expanded connective tissue

摘要: Neuraminidase 1 (NEU1) regulates the catabolism of sialoglycoconjugates in lysosomes. Congenital NEU1 deficiency children is basis sialidosis, a severe neurosomatic disorder which patients experience broad spectrum clinical manifestations varying age onset and severity. Osteoskeletal deformities muscle hypotonia have been described with sialidosis. Here we present first comprehensive analysis skeletal pathology associated loss Neu1 function mice. In this animal model, muscles showed an expansion epimysial perimysial spaces, proliferation fibroblast-like cells abnormal deposition collagens. Muscle fibers located adjacent to expanded connective tissue underwent extensive invagination their sarcolemma, resulted infiltration by extracellular matrix, progressive cytosolic fragmentation. Both juxtaposed infiltrated were strongly positive for lysosomal markers displayed increased proteolytic activity cathepsins metalloproteinases. These combined features could lead remodeling matrix that be responsible sarcolemmal fiber degeneration, ultimately resulting overt atrophic phenotype. This unique pattern damage, has never any myopathy, might explain neuromuscular reported type II form More broadly, these findings point potential role cell remodeling.