Herein, we rescue neonatal lethality in RagA GTP mice and find morphometric and metabolic alterations that span glucose, lipid, ketone, bile acid and amino acid homeostasis in adults, and a median lifespan of nine months.
We have previously shown that constitutive nutrient signaling to mTORC1 by means of genetic activation of RagA (expression of GTP-locked RagA, or RagA GTP) in mice resulted in a fatal energetic crisis at birth. The mechanistic target of rapamycin complex 1 (mTORC1) integrates cellular nutrient signaling and hormonal cues to control metabolism.
Nature Communications volume 12, Article number: 3660 ( 2021) Limited survival and impaired hepatic fasting metabolism in mice with constitutive Rag GTPase signaling
