Conditional Deletion of Translin/Trax in Dopaminergic Neurons Reveals No Impact on Psychostimulant Behaviors or Adiposity
2025
Yunlong Liu | Renkun Wu | Gaiyuan Geng | Helian Yang | Chunmiao Wang | Mengtian Ren | Xiuping Fu
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 <i>Tsn</i> (TN) or <i>Tsnax</i> (TX) using DAT-Cre. Immunostaining confirmed efficient TX loss in <i>Tsnax</i> cKO DA neurons without affecting TN, while <i>Tsn</i> 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 <i>Tsn</i> or <i>Tsnax</i> 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.
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