Verma Vivek, Tan Chay Hoon, Ong Wei Yi, Grigoryan Grigory A, Jones Craig A, Stolzberg Dan, Salvi Richard, Gross Kenneth W, Ratty Anil K, Dawe Gavin S
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Neurosci Res. 2008 Mar;60(3):281-8. doi: 10.1016/j.neures.2007.11.007. Epub 2007 Nov 22.
The chakragati (ckr) mouse, which was serendipitously created as a result of a transgenic insertional mutation, has been proposed as a model of aspects of schizophrenia. The mice exhibit circling, hyperactivity, reduced social interactions, and enlarged lateral ventricles, which parallel aspects of the pathophysiology of schizophrenia. Deficits in sensorimotor gating and processing of the relevance of stimuli are core features of schizophrenia, which underlie many of the symptoms presented. Measures of prepulse inhibition (PPI) and latent inhibition (LI) can assess sensorimotor gating and processing of relevance in both humans and animal models. We investigated PPI of acoustic startle and LI of aversive conditioning in wild-type, heterozygous, and ckr mice. The ckr mice, which are homozygous for the transgene insertion, but not heterozygous littermates, showed impaired PPI in the absence of any difference in acoustic startle amplitude and showed deficits in LI of conditioning of a light stimulus to footshock, measured as suppression of licking for water in water-restricted mice. Together with the previous evidence for hyperactivity, reduced social interactions, and enlarged lateral ventricles, these data lend further support to the suggestion that the ckr mouse has utility as an animal model of aspects of schizophrenia.
Chakragati（ckr）小鼠是由于转基因插入突变而偶然产生的，已被提议作为精神分裂症某些方面的模型。这些小鼠表现出转圈行为、多动、社交互动减少以及侧脑室扩大，这些与精神分裂症病理生理学的某些方面相似。感觉运动门控缺陷和对刺激相关性的处理是精神分裂症的核心特征，是许多所呈现症状的基础。前脉冲抑制（PPI）和潜伏抑制（LI）的测量可以评估人类和动物模型中的感觉运动门控和相关性处理。我们研究了野生型、杂合子和ckr小鼠的听觉惊吓PPI和厌恶性条件反射的LI。转基因插入纯合的ckr小鼠，而非杂合子同窝小鼠，在听觉惊吓幅度无任何差异的情况下表现出PPI受损，并且在光刺激与足部电击条件反射的LI方面存在缺陷，通过限制饮水小鼠舔水抑制来测量。连同先前关于多动、社交互动减少和侧脑室扩大的证据，这些数据进一步支持了ckr小鼠可作为精神分裂症某些方面动物模型的观点。
