ArticleProceedings of the National Academy of Sciences of the United States of America1997
Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 103 citations in OpenAlex.
- GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases.Molecular genetics and metabolism reports · 2025Article
- Deep Learning Cerebellar Magnetic Resonance Imaging Segmentation in Late-Onset GM2 Gangliosidosis: Implications for Phenotype.medRxiv : the preprint server for health sciences · 2025Article
- Gene Therapy Targeting GD3 Synthase Protects Against MPTP-Induced Parkinsonism and Executive Dysfunction.The European journal of neuroscience · 2025Article
- Clinical and biochemical abnormalities in a feline model of GM2 activator deficiency.Molecular genetics and metabolism · 2025Article
- Innate immune sensing of lysosomal dysfunction drives multiple lysosomal storage disorders.Nature cell biology · 2024Article
- Efficacy of Adeno-Associated Virus Serotype 9-Mediated Gene Therapy for AB-Variant GM2 Gangliosidosis.International journal of molecular sciences · 2023Article
- Biochemical Correction of GM2 Ganglioside Accumulation in AB-Variant GM2 Gangliosidosis.International journal of molecular sciences · 2023Article
- Neuronal Ganglioside and Glycosphingolipid (GSL) Metabolism and Disease : Cascades of Secondary Metabolic Errors Can Generate Complex Pathologies (in LSDs).Advances in neurobiology · 2023Article
- Characterization of a phenotypically severe animal model for human AB-Variant GM2 gangliosidosis.Frontiers in molecular neuroscience · 2023Article
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- Therapeutic advantages of combined gene/cell therapy strategies in a murine model of GM2 gangliosidosis.Molecular therapy. Methods & clinical development · 2022Article
- Natural history study of glycan accumulation in large animal models of GM2 gangliosidoses.PloS one · 2020Article
- Dietary Control of Ganglioside Expression in Mammalian Tissues.International journal of molecular sciences · 2019Review
- A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes.Scientific reports · 2019Article
- Lentiviral-mediated knock-down of GD3 synthase protects against MPTP-induced motor deficits and neurodegeneration.Neuroscience letters · 2019Article
- GWAS and network analysis of co-occurring nicotine and alcohol dependence identifies significantly associated alleles and network.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2019Article
- Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study.Molecular genetics and metabolism · 2018Article
- Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice.Journal of visualized experiments : JoVE · 2018Article
- Genetics and Therapies for GM2 Gangliosidosis.Current gene therapy · 2018Review
- Targeted deletion of GD3 synthase protects against MPTP-induced neurodegeneration.Genes, brain, and behavior · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The GM2 activator deficiency (also known as the AB variant), Tay-Sachs disease, and Sandhoff disease are the major forms of the GM2 gangliosidoses, disorders caused by defective degradation of GM2 ganglioside. Tay-Sachs and Sandhoff diseases are caused by mutations in the genes (HEXA and HEXB) encoding the subunits of beta-hexosaminidase A. The GM2 activator deficiency is caused by mutations in the GM2A gene encoding the GM2 activator protein. For degradation of GM2 ganglioside by beta-hexosamindase A, the GM2 activator protein must participate by forming a soluble complex with the ganglioside. In each of the disorders, GM2 ganglioside and related lipids accumulate to pathologic levels in neuronal lysosomes, resulting in clinically similar disorders with an onset in the first year of life, progressive neurodegeneration, and death by early childhood. We previously have described mouse models of Tay-Sachs (Hexa -/-) and Sandhoff (Hexb -/-) diseases with vastly different clinical phenotypes. The Hexa -/- mice were asymptomatic whereas the Hexb -/- mice were severely affected. Through gene disruption in embryonic stem cells we now have established a mouse model of the GM2 activator deficiency that manifests an intermediate phenotype. The Gm2a -/- mice demonstrated neuronal storage but only in restricted regions of the brain (piriform, entorhinal cortex, amygdala, and hypothalamic nuclei) reminiscent of the asymptomatic Tay-Sachs model mice. However, unlike the Tay-Sachs mice, the Gm2a -/- mice displayed significant storage in the cerebellum and defects in balance and coordination. The abnormal ganglioside storage in the Gm2a -/- mice consisted of GM2 with a low amount of GA2. The results demonstrate that the activator protein is required for GM2 degradation and also may indicate a role for the GM2 activator in GA2 degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.