Department of Biochemistry, Laboratory of Neurobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Brazil.
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.
Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1502-1515. doi: 10.1016/j.bbadis.2019.02.022. Epub 2019 Mar 8.
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 mice was increased proliferation of cerebellar granule cell precursors (GCPs). cDNA microarray comparing Nox3 and BALB/c neonatal cerebellum revealed changes in the expression of genes involved in the control of cell proliferation. Nox3 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.
小脑结构和功能的异常可能导致共济失调，这是一种运动协调的神经功能障碍。在本研究过程中，我们对一种具有类似共济失调表型的突变鼠系进行了特征描述。我们将突变定位在 17 号染色体上，并将其映射到 Nox3 基因的 1534 位，导致天冬酰胺 64 到酪氨酸的变化。在 Nox3 小鼠中观察到的主要缺陷是小脑颗粒细胞前体（GCP）的过度增殖。比较 Nox3 和 BALB/c 新生小脑的 cDNA 微阵列显示，参与细胞增殖控制的基因表达发生了变化。Nox3 GCP 和 NSCs 产生更多的活性氧（ROS），并上调 SHH 靶基因的表达，如 Gli1-3 和 Ccnd1（CyclinD1）。我们假设这种新的突变通过刺激 SHH 通路导致增殖增加。我们建议将这种突变鼠系作为一种新的模型来研究 ROS 在神经元前体细胞增殖中的作用。
