Department of Biology, University of Redlands, Redlands, CA 92373, USA.
Behav Brain Res. 2010 Mar 17;208(1):178-88. doi: 10.1016/j.bbr.2009.11.031. Epub 2009 Nov 24.
Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments. The present studies were designed to confirm and expand earlier work on the intriguing behavioral profile of the C58/J inbred strain, including low social approach and aberrant repetitive movements. Additional tests were selected to reflect aspects of autism, a severe neurodevelopmental disorder characterized by emergence of symptoms early in life, higher prevalence in males, social deficits and abnormal repetitive behavior. Mice from the C57BL/6J inbred strain, which has a similar genetic lineage and physical appearance to C58/J, served as a comparison group. Our results revealed that C58/J mice display elevated activity levels by postnatal day 6, which persist into adulthood. Despite normal olfactory ability, young adult male C58/J mice showed deficits in social approach in the three-chambered choice assay and failed to demonstrate social transmission of food preference. In contrast, female C58/J mice performed similarly to female C57BL/6J mice in both social tests. C58/J mice of both sexes demonstrated abnormal repetitive behaviors, displaying excessive jumping and back flipping in both social and non-social situations. These stereotypies were clearly evident in C58/J pups by postnatal days 20-21, and were also observed in C58/J dams during a test for maternal behavior. Overall, the strain profile for C58/J, including spontaneously developing motor stereotypies emerging early in the developmental trajectory, and social deficits primarily in males, models multiple components of the autism phenotype.
具有神经发育障碍相关症状行为表型的小鼠品系可能为测试疾病病因假说和评估潜在治疗方法提供模型。本研究旨在确认和扩展先前关于 C58/J 近交系引人入胜的行为特征的工作,包括社交接近度低和异常重复运动。选择了其他测试来反映自闭症的某些方面,自闭症是一种严重的神经发育障碍,其症状在生命早期出现,男性发病率更高,存在社交缺陷和异常重复行为。C57BL/6J 近交系小鼠作为对照组,与 C58/J 具有相似的遗传谱系和外貌。我们的结果表明,C58/J 小鼠在出生后第 6 天表现出活动水平升高,并持续到成年。尽管嗅觉能力正常,但年轻成年雄性 C58/J 小鼠在三箱选择测试中表现出社交接近缺陷,并且未能表现出食物偏好的社交传递。相比之下,雌性 C58/J 小鼠在这两种社交测试中的表现与雌性 C57BL/6J 小鼠相似。C58/J 小鼠的两性均表现出异常重复行为,在社交和非社交环境中表现出过度跳跃和后空翻。这些刻板行为在出生后第 20-21 天的 C58/J 幼崽中明显可见,在 C58/J 母鼠的母性行为测试中也观察到了这些刻板行为。总的来说,C58/J 品系的特征包括在发育轨迹早期自发出现的运动刻板行为,以及主要在雄性中出现的社交缺陷,该品系模拟了自闭症表型的多个成分。