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

Author(s)

Mazzonetto, P. C. ^[1] ; Ariza, C. B. ^{[1, 2]} ; Ocanha, S. G. ^[1] ; de Souz, T. A. ^[3] ; Ko, G. M. ^[1] ; Menck, C. F. M. ^[3] ; Massironi, S. M. G. ^[4] ; Porcionatto, M. A. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo UNIFESP, Escola Paulista Med, Neurobiol Lab, Dept Biochem, Sao Paulo - Brazil

^[2] Univ Estadual Londrina, Ctr Biol Sci, Dept Gen Pathol, Londrina - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1865, n. 6, p. 1502-1515, JUN 1 2019.
• Web of Science Citations: 0

Abstract

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 Nox.rqm mice was increased proliferation of cerebellar granule cell precursors (GCPs). cDNA microarray comparing Noxrilb and BALB/c neonatal cerebellum revealed changes in the expression of genes involved in the control of cell proliferation. Nox.3`qtb GCPs and NSC produce higher amounts of reactive oxygen species (ROS) and upregulate the expression of SHH target genes, such as Gli1-3 and Ccndl (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. (AU)

• FAPESP's process: 18/05635-8 - Study of cerebellar stem cells and progenitors proliferation stimulated by SHH in mutant mouse for NADPH oxidase 3 (Nox3)
• Grantee: Sarah Gabrielle Ocanha
• Support type: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/19204-8 - Involvement of NOX3 in the control of stem cells / neural precursors proliferation
• Grantee: Patrícia Camacho Mazzonetto
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/25387-2 - Establishment of a next generation sequencing facility as a tool for research in biological systems
• Grantee: Carlos Frederico Martins Menck
• Support type: Regular Research Grants
• FAPESP's process: 17/18765-4 - Role of NOX-produced ROS in the activation of SHH signaling pathway during cerebellar development
• Grantee: Marimélia Aparecida Porcionatto
• Support type: Regular Research Grants