Postnatal expression of Cdkl2 in mouse brain revealed by LacZ inserted into the Cdkl2 locus
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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.
KeywordsCdkl2 KKIAMRE Expression Ontogeny Mutant mice
We thank Drs. M. Hooper, M. Rudnicki, S. Aizawa, K. Yamamura, and T. Curran for kindly providing the E14 ES cell line, Pgk-neo, pMC1DTA, pBlNlacZ, and rat c-Fos cDNA, respectively. We also thank Naoko Nishiyama and Yumi Onodera for excellent technical assistance in the preparation of Cdkl2 mutant mice. T.S. thanks Prof. Koreaki Ito for continuous encouragement.
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