ArticlePloS one2014
Neurologic abnormalities in mouse models of the lysosomal storage disorders mucolipidosis II and mucolipidosis III γ.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026Article
- Age-sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Disruption of Man-6-P-Dependent Sorting to Lysosomes Confers IGF1R-Mediated Apoptosis Resistance.International journal of molecular sciences · 2025Article
- Novel Phenotypical and Biochemical Findings in Mucolipidosis Type II.International journal of molecular sciences · 2025Article
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- Multi-omic analysis of a mucolipidosis II neuronal cell model uncovers involvement of pathways related to neurodegeneration and drug metabolism.Molecular genetics and metabolism · 2024Article
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- Cinnamic acid, a natural plant compound, exhibits neuroprotection in a mouse model of Sandhoff disease via PPARα.NeuroImmune pharmacology and therapeutics · 2024Article
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- CNS Manifestations in Mucolipidosis Type II-A Retrospective Analysis of Longitudinal Data on Neurocognitive Development and Neuroimaging in Eleven Patients.Journal of clinical medicine · 2023Article
- Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Imbalanced cellular metabolism compromises cartilage homeostasis and joint function in a mouse model of mucolipidosis type III gamma.Disease models & mechanisms · 2020Article
- Mucolipidoses Overview: Past, Present, and Future.International journal of molecular sciences · 2020Review
- HumanProceedings of the National Academy of Sciences of the United States of America · 2019Article
- A GNPTAB nonsense variant is associated with feline mucolipidosis II (I-cell disease).BMC veterinary research · 2018Article
- The KASH-containing isoform of Nesprin1 giant associates with ciliary rootlets of ependymal cells.Neurobiology of disease · 2018Article
- Hard X-Ray Nanoholotomography: Large-Scale, Label-Free, 3D Neuroimaging beyond Optical Limit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Article
- GPR56/ADGRG1 regulates development and maintenance of peripheral myelin.The Journal of experimental medicine · 2018Article
- Subcellular Trafficking of Mammalian Lysosomal Proteins: An Extended View.International journal of molecular sciences · 2016Review
- Enzyme-specific differences in mannose phosphorylation between GlcNAc-1-phosphotransferase αβ and γ subunit deficient zebrafish support cathepsin proteases as early mediators of mucolipidosis pathology.Biochimica et biophysica acta · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase is an α2β2γ2 hexameric enzyme that catalyzes the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. Mutations in the α/β subunit precursor gene cause the severe lysosomal storage disorder mucolipidosis II (ML II) or the more moderate mucolipidosis III alpha/beta (ML III α/β), while mutations in the γ subunit gene cause the mildest disorder, mucolipidosis III gamma (ML III γ). Here we report neurologic consequences of mouse models of ML II and ML III γ. The ML II mice have a total loss of acid hydrolase phosphorylation, which results in depletion of acid hydrolases in mesenchymal-derived cells. The ML III γ mice retain partial phosphorylation. However, in both cases, total brain extracts have normal or near normal activity of many acid hydrolases reflecting mannose 6-phosphate-independent lysosomal targeting pathways. While behavioral deficits occur in both models, the onset of these changes occurs sooner and the severity is greater in the ML II mice. The ML II mice undergo progressive neurodegeneration with neuronal loss, astrocytosis, microgliosis and Purkinje cell depletion which was evident at 4 months whereas ML III γ mice have only mild to moderate astrocytosis and microgliosis at 12 months. Both models accumulate the ganglioside GM2, but only ML II mice accumulate fucosylated glycans. We conclude that in spite of active mannose 6-phosphate-independent targeting pathways in the brain, there are cell types that require at least partial phosphorylation function to avoid lysosomal dysfunction and the associated neurodegeneration and behavioral impairments.
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