Mutation in NADPH oxidase 3 (NOX3) impairs SHH signaling and increases cerebellar neural stem/progenitor cell proliferation.

Autor: Mazzonetto PC; Department of Biochemistry, Laboratory of Neurobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Brazil., Ariza CB; Department of Biochemistry, Laboratory of Neurobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Brazil; Department of General Pathology, Center of Biological Sciences, Universidade Estadual de Londrina (UEL), Brazil., Ocanha SG; Department of Biochemistry, Laboratory of Neurobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Brazil., de Souza TA; Department of Microbiology, Institute of Biomedical Sciences, Universidade de São Paulo (USP), Brazil., Ko GM; Department of Biochemistry, Laboratory of Neurobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Brazil., Menck CFM; Department of Microbiology, Institute of Biomedical Sciences, Universidade de São Paulo (USP), Brazil., Massironi SMG; Department of Immunology, Institute of Biomedical Sciences, Universidade de São Paulo (USP), Brazil., Porcionatto MA; Department of Biochemistry, Laboratory of Neurobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Brazil. Electronic address: marimelia.porcionatto@unifesp.br.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2019 Jun 01; Vol. 1865 (6), pp. 1502-1515. Date of Electronic Publication: 2019 Mar 08.
DOI: 10.1016/j.bbadis.2019.02.022
Abstrakt: 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 Nox3 eqlb mice was increased proliferation of cerebellar granule cell precursors (GCPs). cDNA microarray comparing Nox3 eqlb and BALB/c neonatal cerebellum revealed changes in the expression of genes involved in the control of cell proliferation. Nox3 eqlb 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.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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