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TitleGenetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3
Author(s)Garcia, Daniela Raquel Cunha
Fernandes, Daniela Monteiro
Correia, Joana Sofia
Carvalho, Andreia Alexandra Neves
Ferreira, Ana Catarina Coutinho Vilaça
Gomes, Sónia Isabel Nunes Guerra
Viana, João Filipe Oliveira
Oliveira, João F.
Castro, Andreia Cristiana Teixeira
Maciel, P.
Silva, Sara Carina Duarte
Machado–Joseph disease
CMVMJD135 mice
IP3R2 KO mice
Motor behavior
Spinocerebellar ataxias
IP R2 KO mice 3
Issue date25-Jun-2023
PublisherMultidisciplinary Digital Publishing Institute (MDPI)
JournalInternational Journal of Molecular Sciences
CitationCunha-Garcia, D.; Monteiro-Fernandes, D.; Correia, J.S.; Neves-Carvalho, A.; Vilaça-Ferreira, A.C.; Guerra-Gomes, S.; Viana, J.F.; Oliveira, J.F.; Teixeira-Castro, A.; Maciel, P.; et al. Genetic Ablation of Inositol 1,4,5-Trisphosphate Receptor Type 2 (IP3R2) Fails to Modify Disease Progression in a Mouse Model of Spinocerebellar Ataxia Type 3. Int. J. Mol. Sci. 2023, 24, 10606.
Abstract(s)Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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