Abstract：
Axon guidance receptors such as deleted in colorectal cancer (DCC) contribute to the normal formation of neural circuits, and their mutations can be associated with neural defects. In humans, heterozygous mutations in DCC have been linked to congenital mirror movements, which are involuntary movements on one side of the body that mirror voluntary movements of the opposite side. In mice, obvious hopping phenotypes have been reported for bi-allelic Dcc mutations, while heterozygous mutants have not been closely examined. We hypothesized that a detailed characterization of Dcc heterozygous mice may reveal impaired corticospinal and spinal functions. Anterograde tracing of the Dcc +/- motor cortex revealed a normally projecting corticospinal tract, intracortical microstimulation (ICMS) evoked normal contralateral motor responses, and behavioral tests showed normal skilled forelimb coordination. Gait analyses also showed a normal locomotor pattern and rhythm in adult Dcc +/- mice during treadmill locomotion, except for a decreased occurrence of out-of-phase walk and an increased duty cycle of the stance phase at slow walking speed. Neonatal isolated Dcc +/- spinal cords had normal left-right and flexor-extensor coupling, along with normal locomotor pattern and rhythm, except for an increase in the flexor-related motoneuronal output. Although Dcc +/- mice do not exhibit any obvious bilateral impairments like those in humans, they exhibit subtle motor deficits during neonatal and adult locomotion.
摘要：
轴突引导受体如在结直肠癌(DCC)中缺失有助于神经回路的正常形成,它们的突变可能与神经缺陷有关。在人类中,DCC中的杂合突变与先天性镜像运动有关，这是身体一侧的非自愿运动，反映了另一侧的自愿运动。在老鼠身上,已经报道了双等位基因Dcc突变的明显跳跃表型，而杂合突变体尚未经过仔细检查。我们假设Dcc杂合小鼠的详细表征可能揭示皮质脊髓和脊髓功能受损。Dcc+/-运动皮质的顺行追踪显示出正常突出的皮质脊髓束，皮质内微刺激（ICMS）诱发正常的对侧运动反应，行为测试显示前肢协调正常。步态分析还显示，在跑步机运动过程中，成年Dcc/-小鼠的运动模式和节律正常。除了在缓慢的步行速度下，异相步行的发生率降低和站立阶段的占空比增加。新生儿孤立的Dcc+/-脊髓具有正常的左右和屈伸肌耦合，随着正常的运动模式和节奏，除了屈肌相关的运动神经元输出增加。尽管Dcc+/-小鼠不像人类那样表现出任何明显的双侧损伤，他们在新生儿和成人运动期间表现出微妙的运动缺陷。
