The development and interfacing of neuropsychological testing in mice and humans to advance gene investigations into WBS

目前在小鼠中可用的遗传方法使这种生物体对于重要基因的功能分析和用于定义人类疾病发病机制的分子途径是强大的。靠什么？工程学？如果小鼠携带与人类患者相同的遗传缺陷，我们就可以研究由此产生的神经和行为障碍，而这在人类中是不可能的。但是，一些微妙的影响可能会被遗漏，因为目前的老鼠测试可能无法评估正确的行为领域。事实上，人类和老鼠的比较往往是不可能的，因为所使用的任务是完全不同的。关键基因的病理作用被遗漏，可能被排除在大脑发育的研究之外。患有威廉姆斯综合征的个体在运动动作、焦虑、社会行为、学习和记忆方面表现出问题，但已知涉及的不同基因的单独贡献尚不清楚。通过开发尽可能与患者受损的任务相似的任务，并测试携带特定威廉姆斯综合征基因突变的小鼠，我们可以研究每个基因的单独贡献。由此产生的比较将帮助我们确切地了解患者的问题所在，并可能为最终的补救方法提供线索。

Genetic approaches currently available in the mouse make this organism powerful for functional analysis of important genes and for defining molecular pathways underlying the pathogenesis of human disease. By ?engineering? mice to carry the same genetic defects as human patients we can study the resulting neurological and behavioural impairments in ways not possible in humans. But some subtle effects may be missed because current mouse tests may not assess the correct behavioural domains. Indeed human/mouse comparisons are often impossible because the tasks used are completely different. The pathological role of key genes are then missed and may be excluded from investigations into brain development. Individuals with Williams syndrome display problems in motor actions, anxiety, social behaviour, learning and memory, but the separate contributions from the different genes known to be involved are unknown. By developing tasks as similar as possible to those impaired in the patients and testing mice carrying mutations in specific Williams syndrome genes, we can investigate the separate contributions from each gene. The resulting comparisons will help us understand exactly what is going wrong in the patients, and may give clues to eventual remediation methods.