Institute of Medical Genetics and Key Laboratory for Experimental Teratology of Ministry of Education, School of Medicine, Shandong University, Jinan 250012 Shandong, China.
Dis Model Mech. 2013 Mar;6(2):404-13. doi: 10.1242/dmm.009688. Epub 2012 Sep 20.
Mutations in patatin-like phospholipase domain containing 6 (PNPLA6), also known as neuropathy target esterase (NTE) or SPG39, cause hereditary spastic paraplegia (HSP). Although studies on animal models, including mice and Drosophila, have extended our understanding of PNPLA6, its roles in neural development and in HSP are not clearly understood. Here, we describe the generation of a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio). Pnpla6 knockdown resulted in developmental abnormalities and motor neuron defects, including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants were rescued by the introduction of wild-type, but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrate an important role of PNPLA6 in motor neuron development and implicate overexpression of BMP signaling as a possible mechanism underlying the developmental defects in pnpla6 morphants.
PNPLA6 基因突变（也称为神经病靶酯酶[NTE]或 SPG39）可导致遗传性痉挛性截瘫（HSP）。尽管对包括小鼠和果蝇在内的动物模型的研究扩展了我们对 PNPLA6 的理解，但它在神经发育和 HSP 中的作用尚不清楚。在这里，我们使用斑马鱼（Danio rerio）的 morpholino 寡核苷酸敲低来描述 PNPLA6 不足的脊椎动物模型的产生。Pnpla6 敲低导致发育异常和运动神经元缺陷，包括轴突截断和分支。野生型但不是突变型人 PNPLA6 mRNA 的引入挽救了 pnpla6 敲低形态发生体的表型。我们的结果还揭示了 BMP 信号在 pnpla6 敲低表型中的参与。总之，这些结果表明 PNPLA6 在运动神经元发育中起重要作用，并暗示 BMP 信号的过表达可能是 pnpla6 形态发生体发育缺陷的潜在机制。
