Schlett Katalin, Pieri Isabelle, Metzger Friedrich, Marchetti Lara, Steigerwald Frank, Dere Ekrem, Kirilly Dániel, Tárnok Krisztián, Barabás Brigitta, Varga Agnes Kis, Gerspach Jeannette, Huston Josephp, Pfizenmaier Klaus, Köhr Georg, Eisel Ulrich L M
Institute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.
Mol Cell Neurosci. 2004 Nov;27(3):215-26. doi: 10.1016/j.mcn.2004.05.008.
N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granule cells and morphological changes in NR2C/2B cerebellar architecture were already evident from the second postnatal week. Increased NR2B subunit levels led also to a gradual down-regulation of cerebellar NR2A levels, preceding the development of motor impairment in adult animals. Therefore, cerebellar NR2A is important for proper motor coordination and cannot be replaced by long-term expression of NR2B. Consequently, the physiological exchange of NMDA receptor subunits during cerebellar granule cell maturation is important for accurate postnatal development and function.
颗粒细胞中的N-甲基-D-天冬氨酸受体（NMDAR）组成在小脑发育过程中会发生特征性变化。为了分析在出生后第一个月末之前NR2C和NR2A亚基取代NR2B的重要性，我们培育出了持续表达NR2B但缺乏NR2C的小鼠（NR2C-2B小鼠）。突变体表型与NR2C基因敲除小鼠不同，因为从出生后第二周起，颗粒细胞的丢失以及NR2C/2B小脑结构的形态变化就已很明显。NR2B亚基水平的升高还导致成年动物运动障碍出现之前小脑NR2A水平逐渐下调。因此，小脑NR2A对于正常运动协调很重要，不能被NR2B长期表达所取代。因此，小脑颗粒细胞成熟过程中NMDA受体亚基之间的生理性交换对于出生后的准确发育和功能很重要。
