Genetic and functional evidence links tgfbr2 to Nocardia seriolae resistance in spotted sea bass

Spotted sea bass (Lateolabrax maculatus) is an economically important aquaculture species in China, but nocardiosis caused by Nocardia seriolae results in high mortality and economic losses. To investigate the genetic basis of disease resistance, two experimental populations are challenged and analyzed by genome-wide association studies (GWAS). We identify 112 SNPs, including 17 nonsynonymous variants in tgfbr2. Functional enrichment analysis highlights the TGF-β signaling and its related pathways. Structural analysis reveals that TGFBR2 is highly conserved, and mutations in the intracellular kinase domain may alter receptor conformation. Recombinant TGF-β1a modulated splenic lymphocytes transcription, upregulating foxp3b, il10 and smad7, while suppressing proinflammatory cytokines. The tgfbr2 mutation impaires downstream SMAD phosphorylation and reduces transcriptional activation of the foxp3b promoter. These results identify key genetic loci for resistance to N. seriolae and establish a mechanistic connection between TGF-β signaling and immune regulation, providing a foundation for molecular breeding of disease-resistant spotted sea bass.