Abstract
The recently developed Mcoln1(-/-) knockout mouse provides a novel model for analyzing mucolipin 1 function and mucolipidosis type IV disease. Here we characterize the neuropathology of Mcoln1(-/-) mouse at the end stage. Evidence of ganglioside accumulation, including increases in GM2, GM3, and GD3 and redistribution of GM1, was found throughout the central nervous system (CNS) independent of significant cholesterol accumulation. Unexpectedly, colocalization studies using immunofluorescence confocal microscopy revealed that GM1 and GM2 were present in separate vesicles within individual neurons. While GM2 was significantly colocalized with LAMP2, consistent with late-endosomal/lysosomal processing, some GM2-immunoreactivity occurred in LAMP2-negative sites, suggesting involvement of other vesicular systems. P62/Sequestosome 1 (P62/SQSTM1) inclusions were also identified in the CNS of the Mcoln1(-/-) mouse, suggesting deficiencies in protein degradation. Glial cell activation was increased in brain, and there was evidence of reduced myelination in cerebral and cerebellar white matter tracts. Autofluorescent material accumulated throughout the brains of the knockout mice. Finally, axonal spheroids were prevalent in white matter tracts and Purkinje cell axons. This neuropathological characterization of the Mcoln1(-/-) mouse provides an important step in understanding how mucolipin 1 loss of function affects the CNS and contributes to mucolipidosis type IV disease.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Journal of Neuropathology and Experimental Neurology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.