Liu Yunlong, Wu Renkun, Geng Gaiyuan, Yang Helian, Wang Chunmiao, Ren Mengtian, Fu Xiuping
School of Life Sciences and School of Chemistry, Tiangong University, Tianjin 300387, China.
Biomolecules. 2025 Jul 17;15(7):1040. doi: 10.3390/biom15071040.
Despite the abundant expression of the microRNA-degrading Translin (TN)/Trax (TX) complex in midbrain dopaminergic (DA) neurons and its implication in neuropsychiatric disorders, its cell-autonomous roles in metabolic and behavioral responses remain unclear. To address this, we generated DA neuron-specific conditional knockout (cKO) mice for (TN) or (TX) using DAT-Cre. Immunostaining confirmed efficient TX loss in cKO DA neurons without affecting TN, while deletion abolished TX expression, revealing asymmetric protein dependency. Body composition analysis showed no alterations in adiposity in either cKO model. Locomotor responses to acute or repeated administration of cocaine (20 mg/kg) or amphetamine (2.5 mg/kg) were unchanged in or cKO mice. Furthermore, amphetamine-induced conditioned place preference (1 mg/kg) was unaffected. These results demonstrate that the TN/TX complex within DA neurons is dispensable for regulating adiposity, psychostimulant-induced locomotion (both acute and sensitized), or amphetamine reward-related behavior, suggesting its critical functions may lie outside these specific domains.
尽管微小RNA降解蛋白转脂蛋白（TN）/转运蛋白相关蛋白（TX）复合物在中脑多巴胺能（DA）神经元中大量表达，且与神经精神疾病有关，但其在代谢和行为反应中的细胞自主作用仍不清楚。为了解决这个问题，我们使用多巴胺转运体（DAT）-Cre构建了特异性敲除TN或TX的DA神经元条件性敲除（cKO）小鼠。免疫染色证实，TX特异性敲除的cKO DA神经元中TX有效缺失，而不影响TN，而TN缺失则消除了TX的表达，揭示了蛋白的不对称依赖性。身体成分分析显示，两种cKO模型的肥胖情况均无改变。在TN或TX特异性敲除的小鼠中，对急性或重复给予可卡因（20 mg/kg）或苯丙胺（2.5 mg/kg）的运动反应没有变化。此外，苯丙胺诱导的条件性位置偏爱（1 mg/kg）也未受影响。这些结果表明，DA神经元内的TN/TX复合物对于调节肥胖、精神兴奋剂诱导的运动（急性和敏感化）或苯丙胺奖赏相关行为并非必需，提示其关键功能可能存在于这些特定领域之外。
