Comparative Transcriptome Analysis Provides Insights into the Polyunsaturated Fatty Acid Synthesis Regulation of Fat-1 Transgenic Sheep

Transgenic technology has huge application potential in agriculture and medical fields, such as producing new livestock varieties with new valuable features and xenotransplantation. However, how an exogenous gene affects the host animal’s gene regulation networks and their health status is still poorly understood. In the current study, Fat-1 transgenic sheep were generated, and the tissues from 100-day abnormal (DAF_1) and normal (DAF_2) fetuses, postnatal lambs (DAF_4), transgenic-silencing (DAFG5), and -expressing (DAFG6) skin cells were collected and subjected to transcriptome sequencing, and their gene expression profiles were compared in multiple dimensions. The results were as follows. For DAF_1, its abnormal development was caused by pathogen invasion but not the introduction of the Fat-1 gene. Fat-1 expression down-regulated the genes related to the cell cycle; the NF-κB signaling pathway and the PI3K/Akt signaling pathway were down-regulated, and the PUFAs (polyunsaturated fatty acids) biosynthesis pathway was shifted toward the biosynthesis of high-level n-3 LC-PUFAs (long-chain PUFAs). Four key node genes, FADS2, PPARA, PRKACA, and ACACA, were found to be responsible for the gene expression profile shift from the Fat-1 transgenic 100-day fetus to postnatal lamb, and FADS2 may play a key role in the accumulation of n-3 LC-PUFAs in Fat-1 transgenic sheep muscle. Our study provides new insights into the FUFAs synthesis regulation in Fat-1 transgenic animals.