LPIN1基因C236T错义突变影响绵羊尾部脂肪沉积的作用机制

沉积在绵羊尾部的脂肪会影响肉品质、造成饲料浪费且不利于配种，降低养羊业经济效益，因此，研究尾脂的沉积与调控机制具有重要意义。申请者前期研究表明LPIN1基因C236T错义突变显著影响绵羊尾脂，但该突变是通过什么机制影响绵羊尾部脂肪沉积仍未知。前人研究和本人预实验结果表明，LPIN1表达和蛋白结构改变可能影响下游PPAR通路，进而影响尾脂的沉积。本项目首先在细胞水平分析C236T突变在绵羊尾部前脂肪细胞分化过程中对LPIN1及其下游通路基因表达的影响；随后探究C236T是否影响LPIN1蛋白结构与其配体PGC-1α的结合能力和对下游通路信号转导机制；最后制作定点突变Cas9基因编辑大鼠，验证其对脂肪性状的影响。通过以上研究，揭示LPIN1基因C236T突变位点影响尾部脂肪沉积的作用机制，对于了解脂肪沉积及促进C236T作为分子标记在生产中应用具有重要意义。

The fat deposited on the tail of sheep reduces meat quality, causes feed waste and is not conducive to breeding, which is reduce the economic benefits of sheep farming, it is of great significance to study the deposition and regulation mechanism of tail fat. Our previous study showed that the LPIN1 gene C236T missense mutation significantly affected sheep tail fat, but the molecular mechanism of how this mutation affects sheep tail fat deposition is still unknown. Previous studies and my pre-experimental results indicate that LPIN1 expression and protein structure changes may alter tail fat deposition by affect downstream PPAR pathways. This project firstly analyzes the effect of C236T mutation on LPIN1 and its downstream pathway gene expression during the differentiation of sheep tail preadipocytes; then it is investigated whether C236T affects the binding ability of LPIN1 protein structure to its ligand PGC-1α and downstream signal transduction mechanism of the pathway; Finally, a site-directed mutant Cas9 gene editing rat was made to verify its effect on fat traits. Through the above research, revealing the mechanism of LPIN1 gene C236T mutation site affecting tail fat deposition is important for understanding fat deposition and promoting C236T as a molecular marker in production.