Functional Roles and Transcriptional Regulation of Cdkl2/KKIAMRE in Mouse Brain

Cdkl 2编码细胞周期蛋白依赖性激酶样2的转录物在眨眼条件下的兔小脑深核（DCN）中增加。为了研究Cdkl 2在小鼠中的表达模式及其活性依赖性，我们制备了Cdkl 2突变小鼠，其中氨基末端编码外显子使用基因打靶被LacZ取代。LacZ活性首先在出生后第3天至第7天（P3-P7）的大脑皮层中检测到，然后随着年龄的增长逐渐增加，到P28时达到接近最大水平。在成人脑中，在包括嗅球、大脑皮层、海马、丘脑核、杏仁核、膝状体核、红核、小脑深部核、脑神经核和脊髓的各种脑区域的神经元中检测到LacZ活性。lurcher小鼠浦肯野细胞的损失并不影响DCN中LacZ活性的模式和水平。谷氨酸，氯化钾，佛波醇12-肉豆蔻酸酯13-乙酸酯，和白血病抑制因子刺激的初级神经元明显增加c-Fos的水平，但不Cdkl 2转录。这些结果表明cdkl 2主要在成熟神经元中发挥作用，并且小鼠中该基因表达的调控机制与即刻早期基因不同。

Transcripts of Cdkl2 encoding cycline-dependent kinase-like 2 increase in the deep cerebellar nuclei(DCN) of rabbits subjected to eyeblink conditioning. To examine the pattern of Cdkl2 expression and its activity dependence in mice, we prepared Cdkl2 mutant mice in which amino terminal coding exons were replaced by the LacZ using gene targeting. LacZ activity was first detected in the cerebral cortex from postnatal days 3 to 7 (P3-P7), and then gradually increased with age to reach nearly the maximal level by P28. In the adult brain, LacZ activity was detected in neurons in various brain regions including the olfactory bulb, cerebral cortex, hippocampus, thalamic nuclei, amygdaloid nuclei, geniculate nuclei, red nuclei, deep cerebellar nuclei, cranial nerve nuclei, and spinal cord. Loss of Purkinje cells in lurcher mice did not affect the pattern and level of LacZ activity in the DCN. Stimulation of primary neurons with glutamate, KCl, phorbol 12-myristate 13-acetate, and leukemia inhibitory factor appreciably increased the level of c-Fos but not of Cdkl2 transcripts. These results suggest that cdkl2 functions mainly in mature neurons and that mechanisms governing regulation of this gene expression in mice are distinct from those of immediate-early genes.