雏鸡缺硒性胰腺萎缩症（NPA）是家禽特有的一类营养代谢疾病。申请人前期研究证实，日粮缺硒会显著下调细胞铁死亡抑制基因硒蛋白GPX4与雏鸡NPA相关，但是，GPX4介导的细胞铁死亡途径在雏鸡NPA中的具体作用与机制尚需进一步阐明。本项目拟通过建立雏鸡NPA模型，通过定量PCR法和免疫印迹法等方法检测胰腺中GPX4与细胞铁死亡信号通路基因的表达相关性，分析GPX4依赖性铁死亡在NPA中的作用；然后，运用CRISPR/Cas9技术建立GPX4敲除鸡模型，探究细胞铁死亡抑制基因GPX4在NPA中的作用机制；最后，通过注射GPX4 模拟物（mimic）至GPX4敲除鸡检测其缓解NPA的效果，进而论证GPX4在NPA中的作用。研究结果有助于揭示雏鸡NPA发生机制，可为合理使用硒防治雏鸡NPA提供理论依据。

Nutritional pancreatic atrophy (NPA) is a classical Se deficiency disease of poults. Our past study has shown that Se deficiency could significantly down-regulate selenoprotein GPX4, a cell ferroptosis suppressor gene, expression in chicks, which is associated with NPA. However, the mechanism of NPA induced by GPX4 through ferroptosis pathway is unclear. This project intends to use PCR and western blot technologies to identify the relation of GPX4 and ferroptosis signaling pathway genes expression and reveal the role of GPX4 dependent ferroptosis in NPA. Furthermore, CRISPR/Cas9 technology will be used to create GPX4 knockout chickens and to explore the role mechanism of GPX4 dependent ferroptosis in NPA. Finally, the effect of GPX4 mimic injection to GPx4 knockout chickens will demonstrate the role of GPX4 in NPA. These studies will systematically reveal the molecular mechanism for the development of Se-deficiency-induced NPA in chicks and provide new theoretical guidance for developing new nutritional strategies to prevent NPA in chicks.