ArticleHuman molecular genetics2015
Sacs knockout mice present pathophysiological defects underlying autosomal recessive spastic ataxia of Charlevoix-Saguenay.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 99 citations in OpenAlex.
- Loss of SARM1 Improves Phenotypes in a Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Neurology. Genetics · 2026Article
- Alterations in the NaCerebellum (London, England) · 2025Article
- Longitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix-Saguenay Ataxia.Annals of neurology · 2025Article
- Modeling sacsin depletion in Danio Rerio offers new insight on retinal defects in ARSACS.Neurobiology of disease · 2025Article
- Whole Blood DNA Methylation Analysis Reveals Epigenetic Changes Associated with ARSACS.Cerebellum (London, England) · 2025Article
- ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.Cerebellum (London, England) · 2025Review
- A Novel Exon Duplication in theThe application of clinical genetics · 2025Article
- Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay with Early-Onset Epilepsy and Novel Clinical Features:Sultan Qaboos University medical journal · 2025Article
- Genetic modeling of degenerative diseases and mechanisms of neuronal regeneration in the zebrafish cerebellum.Cellular and molecular life sciences : CMLS · 2024Review
- Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin.International journal of molecular sciences · 2024Article
- Driving Mitochondrial Fission Improves Cognitive, but not Motor Deficits in a Mouse Model of Ataxia of Charlevoix-Saguenay.Cerebellum (London, England) · 2024Article
- Structured connectivity in the output of the cerebellar cortex.Nature communications · 2024Article
- Compound Heterozygous Mutations ofInternational journal of molecular sciences · 2024Article
- Driving mitochondrial fission improves cognitive, but not motor deficits in a mouse model of Ataxia of Charlevoix-Saguenay.Research square · 2024Article
- A Novel Mutation in Sacsin, p.Val1335IIe, May Cause Late-Onset Sacsinopathy Due to Haploinsufficiency.Current issues in molecular biology · 2023Article
- A SACS deletion variant in Great Pyrenees dogs causes autosomal recessive neuronal degeneration.Human genetics · 2023Article
- Restoring calcium homeostasis in Purkinje cells arrests neurodegeneration and neuroinflammation in the ARSACS mouse model.JCI insight · 2023Article
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- In Vitro Characterization of Motor Neurons and Purkinje Cells Differentiated from Induced Pluripotent Stem Cells Generated from Patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Stem cells international · 2023Article
- The J Domain of Sacsin Disrupts Intermediate Filament Assembly.International journal of molecular sciences · 2022Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS [MIM 270550]) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. Over 170 SACS mutations have been reported worldwide and are thought to cause loss of function of sacsin, a poorly characterized and massive 520 kDa protein. To establish an animal model and to examine the pathophysiological basis of ARSACS, we generated Sacs knockout (Sacs(-/-)) mice. Null animals displayed an abnormal gait with progressive motor, cerebellar and peripheral nerve dysfunctions highly reminiscent of ARSACS. These clinical features were accompanied by an early onset, progressive loss of cerebellar Purkinje cells followed by spinal motor neuron loss and peripheral neuropathy. Importantly, loss of sacsin function resulted in abnormal accumulation of non-phosphorylated neurofilament (NF) bundles in the somatodendritic regions of vulnerable neuronal populations, a phenotype also observed in an ARSACS brain. Moreover, motor neurons cultured from Sacs(-/-) embryos exhibited a similar NF rearrangement with significant reduction in mitochondrial motility and elongated mitochondria. The data points to alterations in the NF cytoskeleton and defects in mitochondrial dynamics as the underlying pathophysiological basis of ARSACS.
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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.