ArticleHuman molecular genetics2013
Reduction of mutant ataxin-7 expression restores motor function and prevents cerebellar synaptic reorganization in a conditional mouse model of SCA7.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Purkinje cell intrinsic activity shapes cerebellar development and function.Nature communications · 2026Article
- Article
- The Molecular Basis of Spinocerebellar Ataxia Type 7.Frontiers in neuroscience · 2022Review
- A Subpopulation of Microglia Generated in the Adult Mouse Brain Originates from Prominin-1-Expressing Progenitors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- SCA7 Mouse Cerebellar Pathology Reveals Preferential Downregulation of Key Purkinje Cell-Identity Genes and Shared Disease Signature with SCA1 and SCA2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Cerebellar developmental deficits underlie neurodegenerative disorder spinocerebellar ataxia type 23.Brain pathology (Zurich, Switzerland) · 2021Article
- Article
- TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons.eLife · 2020Article
- Task Force Paper On Cerebellar Transplantation: Are We Ready to Treat Cerebellar Disorders with Cell Therapy?Cerebellum (London, England) · 2019Review
- Motor Performances of Spontaneous and Genetically Modified Mutants with Cerebellar Atrophy.Cerebellum (London, England) · 2019Review
- Antisense oligonucleotides targeting mutant Ataxin-7 restore visual function in a mouse model of spinocerebellar ataxia type 7.Science translational medicine · 2018Article
- Spinocerebellar ataxias: prospects and challenges for therapy development.Nature reviews. Neurology · 2018Review
- Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases.Acta neuropathologica · 2017Article
- Article
- Transplantation and Stem Cell Therapy for Cerebellar Degenerations.Cerebellum (London, England) · 2016Review
- Experimental neurotransplantation treatment for hereditary cerebellar ataxias.Cerebellum & ataxias · 2016Review
- MULTIMODAL IMAGING OF A FAMILY WITH SPINOCEREBELLAR ATAXIA TYPE 7 DEMONSTRATING PHENOTYPIC VARIATION AND PROGRESSION OF RETINAL DEGENERATION.Retinal cases & brief reports · 2016Article
- An understanding of spinocerebellar ataxia.The Indian journal of medical research · 2015Article
- Abnormal climbing fibre-Purkinje cell synaptic connections in the essential tremor cerebellum.Brain : a journal of neurology · 2014Article
- Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse model of SCA7.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Spinocerebellar ataxia type 7 (SCA7) is a dominantly inherited neurodegenerative disorder caused by a CAG - polyglutamine (polyQ) repeat expansion in the ataxin-7 gene. In polyQ disorders, synaptic dysfunction and neurodegeneration may develop prior to symptom onset. However, conditional expression studies of polyQ disease models demonstrate that suppression of gene expression can yield complete reversal of established behavioral abnormalities. To determine if SCA7 neurological and neurodegenerative phenotypes are reversible, we crossed PrP-floxed-SCA7-92Q BAC transgenic mice with a tamoxifen-inducible Cre recombinase transgenic line, CAGGS-Cre-ER™. PrP-floxed-SCA7-92Q BAC;CAGGS-Cre-ER™ bigenic mice were treated with a single dose of tamoxifen 1 month after the onset of detectable ataxia, which resulted in ~50% reduction of polyQ-ataxin-7 expression. Tamoxifen treatment halted or reversed SCA7 motor symptoms, reduced ataxin-7 aggregation in Purkinje cells (PCs), and prevented loss of climbing fiber (CF)-PC synapses in comparison to vehicle-treated bigenic animals and tamoxifen-treated PrP-floxed-SCA7-92Q BAC single transgenic mice. Despite this phenotype rescue, reduced ataxin-7 expression did not result in full recovery of cerebellar molecular layer thickness or prevent Bergmann glia degeneration. These results demonstrate that suppression of mutant gene expression by only 50% in a polyQ disease model can have a significant impact on disease phenotypes, even when initiated after the onset of detectable behavioral deficits. The findings reported here are consistent with the emerging view that therapies aimed at reducing neurotoxic gene expression hold the potential to halt or reverse disease progression in afflicted patients, even after the onset of neurological disability.
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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.