Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Int J Mol Sci. 2017 Dec 29;19(1):97. doi: 10.3390/ijms19010097.
Rett Syndrome (RTT), an autism-related disorder caused by mutation of the X-linked Methyl CpG-binding Protein 2 () gene, is characterized by severe cognitive and intellectual deficits. While cognitive deficits are well-documented in humans and rodent models, impairments of sensory, motor and metabolic functions also occur but remain poorly understood. To better understand non-cognitive deficits in RTT, we studied female rats heterozygous for mutation (); unlike commonly used male rodent models, this more closely approximates human RTT where males rarely survive. rats showed rapid, progressive decline of motor coordination through six months of age as assessed by rotarod performance, accompanied by deficits in gait and posture. rats were hyper-responsive to noxious pressure and cold, but showed visceral hyposensitivity when tested by colorectal distension. rats ate less, drank more, and had more body fat resulting in increased weight gain. Our findings reveal an array of progressive non-cognitive deficits in this rat model that are likely to contribute to the compromised quality of life that characterizes RTT.
雷特综合征（RTT）是一种与自闭症相关的疾病，由 X 连锁的甲基 CpG 结合蛋白 2（）基因突变引起，其特征是严重的认知和智力缺陷。虽然人类和啮齿动物模型中已经有认知缺陷的相关记载，但感官、运动和代谢功能的损伤也同样存在，只是尚未得到充分理解。为了更好地了解 RTT 中的非认知缺陷，我们研究了携带突变（）的杂合子雌性大鼠（）；与常用的雄性 啮齿动物模型不同，这种模型更接近男性很少存活的人类 RTT。大鼠在 6 个月大时，通过转棒试验表现出运动协调能力的快速、进行性下降，同时还存在步态和姿势缺陷。大鼠对有害压力和寒冷反应过度，但在结肠扩张试验中，对内脏的敏感性降低。大鼠的食量减少，饮水量增加，体脂增加，导致体重增加。我们的研究结果揭示了这种大鼠模型中一系列进行性的非认知缺陷，这些缺陷可能导致 RTT 患者生活质量受损。
