Cytosolic 5′-nucleotidases II (cNT5-II) are an evolutionary conserved family of 5′-nucleotidases that catalyze the intracellular hydrolysis of nucleotides. In humans, the family is encoded by five genes, namely NT5C2, NT5DC1, NT5DC2, NT5DC3, and NT5DC4. While very little is known about the role of these genes in the nervous system, several of them have been associated with neuropsychiatric disorders. Here, we tested whether manipulating neuronal expression of cNT5-II orthologues affects neuropsychiatric disorders-related phenotypes in the model organism Drosophila melanogaster. We investigated the brain expression of Drosophila orthologues of cNT5-II family (dNT5A-CG2277, dNT5B-CG32549, and dNT5C-CG1814) using quantitative real-time polymerase chain reaction (qRT-PCR). Using the UAS/Gal4 system, we also manipulated the expression of these genes specifically in neurons. The knockdown was subjected to neuropsychiatric disorder-relevant behavioral assays, namely light-off jump reflex habituation and locomotor activity, and sleep was measured. In addition, neuromuscular junction synaptic morphology was assessed. We found that dNT5A, dNT5B, and dNT5C were all expressed in the brain. dNT5C was particularly enriched in the brain, especially at pharate and adult stages. Pan-neuronal knockdown of dNT5A and dNT5C showed impaired habituation learning. Knockdown of each of the genes also consistently led to mildly reduced activity and/or increased sleep. None of the knockdown models displayed significant alterations in synaptic morphology. In conclusion, in addition to genetic associations with psychiatric disorders in humans, altered expression of cNT5-II genes in the Drosophila nervous system plays a role in disease-relevant behaviors.

胞质5'-核苷酸酶II（cNT5-II）是进化保守的5'-核苷酸酶家族，可催化​​核苷酸的胞内水解。在人类中，该家族由五个基因编码，即NT5C2，NT5DC1，NT5DC2，NT5DC3和NT5DC4。尽管对这些基因在神经系统中的作用了解甚少，但其中一些与神经精神疾病有关。在这里，我们测试了在模型生物果蝇中是否操纵cNT5-II直向同源物的神经元表达会影响与神经精神疾病相关的表型。我们研究了果蝇的大脑表达cNT5-II家族的直向同源物（dNT5A - CG2277，dNT5B - CG32549和dNT5C-CG1814）使用实时定量聚合酶链反应（qRT-PCR）。使用UAS / Gal4系统，我们还操纵了这些基因在神经元中的表达。对击倒者进行与神经精神疾病有关的行为分析，即起跳跳跃习惯和运动活动，并测量睡眠。此外，评估了神经肌肉连接突触的形态。我们发现dNT5A，dNT5B和dNT5C都在大脑中表达。dNT5C尤其是在阶段性和成年期时，大脑尤其丰富。dNT5A和dNT5C的泛神经元敲低表明习性学习受损。每个基因的基因敲除也始终导致轻度降低的活动和/或增加的睡眠。击倒模型均未显示突触形态的显着改变。总之，除了与人类精神疾病的遗传关联外，果蝇神经系统中cNT5-II基因表达的改变在与疾病相关的行为中也起作用。