| First Author | Deng Y | Year | 2021 |
| Journal | J Neuroinflammation | Volume | 18 |
| Issue | 1 | Pages | 107 |
| PubMed ID | 33957945 | Mgi Jnum | J:329598 |
| Mgi Id | MGI:6811846 | Doi | 10.1186/s12974-021-02153-8 |
| Citation | Deng Y, et al. (2021) Conditional knockout of Tsc1 in RORgammat-expressing cells induces brain damage and early death in mice. J Neuroinflammation 18(1):107 |
| abstractText | BACKGROUND: Tuberous sclerosis complex 1 (Tsc1) is known to regulate the development and function of various cell types, and RORgammat is a critical transcription factor in the immune system. However, whether Tsc1 participates in regulating RORgammat-expressing cells remains unknown. METHODS: We generated a mouse model in which Tsc1 was conditionally deleted from RORgammat-expressing cells (Tsc1(RORgammat)) to study the role of RORgammat-expressing cells with Tsc1 deficiency in brain homeostasis. RESULTS: Type 3 innate lymphoid cells (ILC3s) in Tsc1(RORgammat) mice displayed normal development and function, and the mice showed normal Th17 cell differentiation. However, Tsc1(RORgammat) mice exhibited spontaneous tonic-clonic seizures and died between 4 and 6 weeks after birth. At the age of 4 weeks, mice in which Tsc1 was specifically knocked out in RORgammat-expressing cells had cortical neuron defects and hippocampal structural abnormalities. Notably, over-activation of neurons and astrogliosis were observed in the cortex and hippocampus of Tsc1(RORgammat) mice. Moreover, expression of the gamma-amino butyric acid (GABA) receptor in the brains of Tsc1(RORgammat) mice was decreased, and GABA supplementation prolonged the lifespan of the mice to some extent. Further experiments revealed the presence of a group of rare RORgammat-expressing cells with high metabolic activity in the mouse brain. CONCLUSIONS: Our study verifies the critical role of previously unnoticed RORgammat-expressing cells in the brain and demonstrates that the Tsc1 signaling pathway in RORgammat-expressing cells is important for maintaining brain homeostasis. |
