The role of the integrated stress response pathway on amino acid regulation of murine lactation

Abstract

Essential amino acids are the substrate for milk protein synthesis in the mammary gland. However, some amino acids play a supplementary role by signaling on cellular pathways that regulate lactation. The integrated stress response pathway, through GCN2, senses unacetylated tRNAs and correspondingly inhibits protein translation initiation. We hypothesize that a GCN2 depleted mouse would not respond to protein restriction, it would maintain the level of milk production of a non-restricted mouse, thus utilizing dietary protein more efficiently. In this experiment, we used a genetic model in which GCN2 is deleted in mammary epithelial cells during lactation. Then, we restricted dietary protein in both, wild type and GCN2 knockout dams. We determined that GCN2 seems to be a minor factor on lactation with regard to protein output in a murine model.