Gerlai R, Roder J
Mount Sinai Hospital Research Institute, Division of Molecular Immunology and Neurobiology, Toronto, Ontario, Canada.
J Psychiatry Neurosci. 1995 Mar;20(2):105-12.
S100 beta, a calcium-binding brain protein, has been implicated in brain development and hippocampal neurophysiology including long-term potentiation. Its gene maps to chromosome 21, which is duplicated in Down syndrome. S100 beta levels are elevated in both Down syndrome and Alzheimer's disease, human neurodegenerative diseases associated with mental retardation and dementia. To investigate whether or not elevated S100 beta levels can cause brain dysfunctioning in mammals, transgenic mice carrying multiple copies of the human S100 beta gene were generated. Several independent lines of transgenic mice were compared to age-matched normal control mice of identical genetic background (CD1) by measuring their exploratory behaviors in novel situations. Transgenic mice exhibited a range of defects including female specific hyperactivity, lack of habituation to novelty and reduced T-maze spontaneous alternation rate. Although the neuroanatomical or physiological substrate of these abnormalities is unknown, they are similar to the behavioral manifestations of hippocampal dysfunction. The S100 beta mouse offers one of the first opportunities to investigate the relationship between over-expression of a human chromosome 21 gene product and abnormal behavior and brain functioning.
S100β是一种与钙结合的脑蛋白，它与脑发育以及包括长时程增强在内的海马神经生理学有关。其基因定位于21号染色体，而在唐氏综合征中该染色体会发生重复。在唐氏综合征和阿尔茨海默病（与智力迟钝和痴呆相关的人类神经退行性疾病）中，S100β水平均会升高。为了研究升高的S100β水平是否会导致哺乳动物脑功能异常，研究人员培育了携带多个拷贝人类S100β基因的转基因小鼠。通过测量在新环境中的探索行为，将几个独立品系的转基因小鼠与年龄匹配的具有相同遗传背景（CD1）的正常对照小鼠进行比较。转基因小鼠表现出一系列缺陷，包括雌性特异性多动、对新事物缺乏习惯化以及T迷宫自发交替率降低。尽管这些异常的神经解剖学或生理学基础尚不清楚，但它们类似于海马功能障碍的行为表现。S100β小鼠为研究人类21号染色体基因产物的过度表达与异常行为及脑功能之间的关系提供了首批机会之一。
