Dars2-flox Mouse

DARS2, encoding mitochondrial aspartyl-tRNA synthetase, is a pivotal member of the Aminoacyl-tRNA synthetases family crucial for protein translation regulation [2]. Mutations in DARS2 can lead to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL), a rare neurological disorder [4,5,6].

In cancer research, DARS2 has emerged as a significant factor. In lung adenocarcinoma (LUAD), its expression is upregulated, correlating with tumor stage and poor prognosis. Knockdown and overexpression studies in LUAD cells showed that DARS2 affects cell proliferation, invasion, and migration both in vitro and in vivo, acting via the ERK/c-Myc signaling pathway [1]. In bladder cancer, DARS2 is also upregulated, promoting cell proliferation, metastasis, and immune escape, potentially by modulating PD-L1 [2]. Additionally, in bladder cancer, DARS2 promotes the G1-to-S phase transition and enhances PINK1-mediated mitophagy, driving tumor progression [3].

In conclusion, DARS2 is essential for normal cellular function, especially in protein translation. Its mutations are linked to LBSL. In cancer, particularly LUAD and bladder cancer, DARS2 plays oncogenic roles, promoting tumor cell growth, invasion, and metastasis. Research on DARS2, including through gene knockout or conditional knockout models, has enhanced our understanding of its functions in disease, offering potential for new biomarker discovery and therapeutic strategies.