DISRUPTED MEMBRANE HOMEOSTASIS AND ACCUMULATION OF UBIQUITINATED PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 最近在婴儿神经轴索营养不良(INAD)和伴有脑铁积聚的神经变性患者中发现了PLA2G6基因的突变，PLA2G6基因通过钙非依赖性磷脂酶A2(iPLA2(2)beta)编码组。这些儿童神经退行性疾病的一个病理特征是在远端轴突中存在独特的球体，其中包含积聚的膜。我们使用同源重组产生的iPLA(2)β-KO小鼠来研究PLA2G6突变的神经退行性后果。Ipla(2)β-KO小鼠在13个月大时出现年龄依赖性神经损伤，在旋转、平衡和攀登测试中表现明显。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mutations in the PLA2G6 gene, which encodes group VIA calcium-independent phospholipase A2 (iPLA(2)beta), were recently identified in patients with infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation. A pathological hallmark of these childhood neurodegenerative diseases is the presence of distinctive spheroids in distal axons that contain accumulated membranes. We used iPLA(2)beta-KO mice generated by homologous recombination to investigate neurodegenerative consequences of PLA2G6 mutations. iPLA(2)beta-KO mice developed age-dependent neurological impairment that was evident in rotarod, balance, and climbing tests by 13 months of age.