Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19. The 22 studies included in the review (from a total of 1281 identified records) show that the behavioral phenotype of the ClockΔ19 mouse is characterized by hyperactivity, decreased anxiety-like behavior, decreased depression-like behavior and increased preference for rewarding stimuli. This is highly consistent with mania in humans. Moreover, the ClockΔ19 mouse exhibits rapid mood cycling (a manic-like phenotype during the day followed by euthymia at night), which is consistent with BD. Chronic administration of lithium, a drug with well established mood-stabilizing effect in humans with BD, reverses the majority of the bipolar-like traits and most of the neurobiological abnormalities observed in the ClockΔ19 mouse. In conclusion, the ClockΔ19 mouse has substantial face validity as an animal model for BD. The predictive validity of the ClockΔ19 mouse has primarily been investigated via studies using lithium challenge. Therefore, further studies are needed to determine how the ClockΔ19 mouse responds to other mood-stabilizing treatments of BD such as valproate, lamotrigine, carbamazepine, oxcarbazepine, antipsychotics, electroconvulsive therapy and various light interventions.

中文翻译：

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ClockΔ19 小鼠作为双相情感障碍动物模型的面部和预测有效性：系统评价。

携带昼夜节律运动输出周期 Kaput delta 19 N-乙基-N-亚硝基 (ENU) 突变 (ClockΔ19) 的小鼠被用作双相情感障碍 (BD) 的动物模型。我们的目的是按照系统评价和荟萃分析的首选报告项目 (PRISMA) 指南，系统地评价该模型的表面有效性（与 BD 的表型和病理生理学相似性）和预测有效性（对 BD 中使用的治疗的反应性）。我们对 PubMed 和 Embase 数据库进行了系统检索，结合了 BD 和 ClockΔ19 的检索词。审查中包含的 22 项研究（总共 1281 条已识别记录）表明，ClockΔ19 小鼠的行为表型的特点是多动、焦虑样行为减少、抑郁样行为减少以及对奖励刺激的偏好增加。这与人类的躁狂症高度一致。此外，ClockΔ19 小鼠表现出快速的情绪循环（白天出现躁狂样表型，然后在晚上出现情绪正常），这与 BD 一致。锂是一种对双相情感障碍患者具有良好的情绪稳定作用的药物，长期服用锂可以逆转在 ClockΔ19 小鼠中观察到的大多数双相情感障碍样特征和大多数神经生物学异常。总之，ClockΔ19 小鼠作为 BD 动物模型具有显着的表面效度。ClockΔ19 小鼠的预测有效性主要通过使用锂挑战的研究进行了调查。因此，需要进一步的研究来确定 ClockΔ19 小鼠对其他 BD 情绪稳定治疗（如丙戊酸盐、拉莫三嗪、卡马西平、奥卡西平、抗精神病药物、电惊厥治疗和各种光干预）的反应。