The cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (CYFIP2) gene is associated with epilepsy, intellectual disability (ID), and developmental delay, suggesting its critical role in proper neuronal development and function. CYFIP2 is involved in regulating cellular actin dynamics and also interacts with RNA-binding proteins. However, the adult brain function of CYFIP2 remains unclear because investigations thus far are limited to Cyfip2 heterozygous (Cyfip2^+/−) mice owing to the perinatal lethality of Cyfip2-null mice. Therefore, we generated Cyfip2 conditional knock-out (cKO) mice with reduced CYFIP2 expression in postnatal forebrain excitatory neurons (CaMKIIα-Cre). We found that in the medial prefrontal cortex (mPFC) of adult Cyfip2 cKO mice, CYFIP2 expression was decreased in both layer 2/3 (L2/3) and layer 5 (L5) neurons, unlike the L5-specific CYFIP2 reduction observed in adult Cyfip2^+/− mice. Nevertheless, filamentous actin (F-actin) levels were increased only in L5 of Cyfip2 cKO mPFC possibly because of a compensatory increase in CYFIP1, the other member of CYFIP family, in L2/3 neurons. Abnormal dendritic spines on basal, but not on apical, dendrites were consistently observed in L5 neurons of Cyfip2 cKO mPFC. Meanwhile, neuronal excitability and activity were enhanced in both L2/3 and L5 neurons of Cyfip2 cKO mPFC, suggesting that CYFIP2 functions of regulating F-actin and excitability/activity may be mediated through independent mechanisms. Unexpectedly, adult Cyfip2 cKO mice did not display locomotor hyperactivity or reduced anxiety observed in Cyfip2^+/− mice. Instead, both exhibited enhanced social dominance accessed by the tube test. Together, these results provide additional insights into the functions of CYFIP2 in the adult brain.

胞质脆性X智力低下1（FMR1）相互作用蛋白2（CYFIP2）基因与癫痫，智力障碍（ID）和发育延迟有关，表明其在适当的神经元发育和功能中起关键作用。CYFIP2参与调节细胞肌动蛋白的动力学，并且还与RNA结合蛋白相互作用。但是，CYFIP2的成人脑功能仍不清楚，因为迄今为止的研究仅限于Cyfip2 杂合的（Cyfip2 ^+/-）小鼠由于其围产期致死性 Cyfip2-空小鼠。因此，我们产生了Cyfip2 CYPIP2在产后前脑兴奋性神经元中表达降低的条件敲除（cKO）小鼠（CaMKIIα-Cre）。我们发现在成人的内侧前额叶皮层（mPFC）Cyfip2 cKO小鼠，CYFIP2表达在第2/3层（L2 / 3）和第5层（L5）神经元中均降低，这与成人中观察到的L5特异性CYFIP2降低不同 Cyfip2 ^+/-老鼠。然而，丝状肌动蛋白（F-肌动蛋白）水平仅在L5的L5中升高。Cyfip2cKO mPFC可能是由于CYFIP家族另一成员CYFIP1在L2 / 3神经元中的代偿性增加。持续观察到L5神经元的基础上的树突棘异常，而在根尖上没有观察到。Cyfip2cKO mPFC。同时，L2 / 3和L5神经元的神经元兴奋性和活性均增强。Cyfip2cKO mPFC，提示CYFIP2调节F-肌动蛋白和兴奋性/活性的功能可能是通过独立的机制介导的。没想到，大人Cyfip2 cKO小鼠没有表现出运动亢进或减轻焦虑。 Cyfip2 ^+/-老鼠。取而代之的是，两者都显示出通过试管测试获得的增强的社会主导地位。在一起，这些结果为成人大脑中CYFIP2的功能提供了更多的见解。