The signaling scaffold protein GIT1 is expressed widely throughout the brain, but its function in vivo remains elusive. Mice lacking GIT1 have been proposed as a model for attention deficit-hyperactivity disorder, due to alterations in basal locomotor activity as well as paradoxical locomotor suppression by the psychostimulant amphetamine. Since we had previously shown that GIT1-knockout mice have normal locomotor activity, here we examined GIT1-deficient mice for ADHD-like behavior in more detail, and find neither hyperactivity nor amphetamine-induced locomotor suppression. Instead, GIT1-deficient mice exhibit profound learning and memory defects and reduced synaptic structural plasticity, consistent with an intellectual disability phenotype. We conclude that loss of GIT1 alone is insufficient to drive a robust ADHD phenotype in distinct strains of mice. In contrast, multiple learning and memory defects have been observed here and in other studies using distinct GIT1-knockout lines, consistent with a predominant intellectual disability phenotype related to altered synaptic structural plasticity.

信号支架蛋白GIT1在整个大脑中广泛表达，但其在体内的功能仍然难以捉摸。缺乏GIT1的小鼠已被提出作为注意力缺陷多动障碍的模型，这是由于基础运动活性的改变以及精神刺激性苯丙胺对矛盾运动的抑制。由于我们以前已经证明了GIT1敲除小鼠具有正常的运动功能，因此在这里我们更详细地检查了GIT1缺陷小鼠的ADHD样行为，并且既未发现过度活跃，也未发现苯丙胺诱导的运动抑制。相反，GIT1缺陷小鼠表现出深刻的学习和记忆缺陷，突触结构可塑性降低，与智力残疾表型一致。我们得出的结论是，单独的GIT1缺失不足以在不同的小鼠品系中驱动强大的ADHD表型。相比之下，