Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA.
Neuroscience. 2011 Sep 8;190:398-408. doi: 10.1016/j.neuroscience.2011.06.010. Epub 2011 Jun 13.
The dyslexia-associated gene DCDC2 is a member of the DCX family of genes known to play roles in neurogenesis, neuronal migration, and differentiation. Here we report the first phenotypic analysis of a Dcdc2 knockout mouse. Comparisons between Dcdc2 knockout mice and wild-type (wt) littermates revealed no significant differences in neuronal migration, neocortical lamination, neuronal cilliogenesis or dendritic differentiation. Considering previous studies showing genetic interactions and potential functional redundancy among members of the DCX family, we tested whether decreasing Dcx expression by RNAi would differentially impair neurodevelopment in Dcdc2 knockouts and wild-type mice. Consistent with this hypothesis, we found that deficits in neuronal migration, and dendritic growth caused by RNAi of Dcx were more severe in Dcdc2 knockouts than in wild-type mice with the same transfection. These results indicate that Dcdc2 is not required for neurogenesis, neuronal migration or differentiation in mice, but may have partial functional redundancy with Dcx.
与阅读障碍相关的基因 DCDC2 是 DCX 基因家族的成员，已知该基因家族在神经发生、神经元迁移和分化中发挥作用。本文报道了 Dcdc2 敲除小鼠的首个表型分析。Dcdc2 敲除小鼠与野生型（wt）同窝仔鼠之间的比较显示，神经元迁移、新皮质分层、神经元纤毛发生或树突分化均无显著差异。考虑到先前的研究表明 DCX 家族成员之间存在遗传相互作用和潜在的功能冗余，我们测试了通过 RNAi 降低 Dcx 的表达是否会在 Dcdc2 敲除和野生型小鼠中差异地损害神经发育。与这一假说一致，我们发现，与具有相同转染的野生型小鼠相比，RNAi 下调 Dcx 导致的神经元迁移和树突生长缺陷在 Dcdc2 敲除小鼠中更为严重。这些结果表明，Dcdc2 对于小鼠的神经发生、神经元迁移或分化并非必需，但可能与 Dcx 具有部分功能冗余。
