Mutation in NADPH oxidase 3 (NOX3) impairs SHH signaling and increases cerebellar neural stem/progenitor cell proliferation
| Autor: | Gui Mi Ko, Silvia Maria Gomes Massironi, Carlos Frederico Martins Menck, Carolina Batista Ariza, S.G. Ocanha, Marimelia Porcionatto, P.C. Mazzonetto, T.A. de Souza |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cerebellum Mutant Primary Cell Culture Nerve Tissue Proteins Motor Activity Zinc Finger Protein Gli2 medicine.disease_cause Zinc Finger Protein GLI1 03 medical and health sciences Mice 0302 clinical medicine Neural Stem Cells Zinc Finger Protein Gli3 medicine Animals Cyclin D1 Hedgehog Proteins Sonic hedgehog Progenitor cell Molecular Biology Cell Proliferation Mice Knockout Mutation Mice Inbred BALB C NADPH oxidase biology Cell growth Gene Expression Profiling Chromosome Mapping Gene Expression Regulation Developmental NADPH Oxidases Cell Differentiation Granule cell Chromosomes Mammalian Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure biology.protein Molecular Medicine Ataxia Reactive Oxygen Species 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Biochimica et biophysica acta. Molecular basis of disease. 1865(6) |
| ISSN: | 1879-260X |
| Popis: | Abnormalities in cerebellar structure and function may cause ataxia, a neurological dysfunction of motor coordination. In the course of the present study, we characterized a mutant mouse lineage with an ataxia-like phenotype. We localized the mutation on chromosome 17 and mapped it to position 1534 of the Nox3 gene, resulting in p.Asn64Tyr change. The primary defect observed in Nox3eqlb mice was increased proliferation of cerebellar granule cell precursors (GCPs). cDNA microarray comparing Nox3eqlb and BALB/c neonatal cerebellum revealed changes in the expression of genes involved in the control of cell proliferation. Nox3eqlb GCPs and NSC produce higher amounts of reactive oxygen species (ROS) and upregulate the expression of SHH target genes, such as Gli1-3 and Ccnd1 (CyclinD1). We hypothesize that this new mutation is responsible for an increase in proliferation via stimulation of the SHH pathway. We suggest this mutant mouse lineage as a new model to investigate the role of ROS in neuronal precursor cell proliferation. |
| Databáze: | OpenAIRE |
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