Sprengel R, Suchanek B, Amico C, Brusa R, Burnashev N, Rozov A, Hvalby O, Jensen V, Paulsen O, Andersen P, Kim J J, Thompson R F, Sun W, Webster L C, Grant S G, Eilers J, Konnerth A, Li J, McNamara J O, Seeburg P H
Max-Planck Institute for Medical Research, Department of Molecular Neuroscience, Heidelberg, Germany.
Cell. 1998 Jan 23;92(2):279-89. doi: 10.1016/s0092-8674(00)80921-6.
NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.
N-甲基-D-天冬氨酸（NMDA）受体是一类具有高钙离子传导性的谷氨酸门控阳离子通道，介导中枢兴奋性突触的快速传递和可塑性。我们在此表明，基因靶向小鼠表达的NMDA受体缺失三个NR2亚基中任何一个的大的细胞内C末端结构域，其表型类似于该特定亚基缺失的小鼠。以C末端截短形式表达NR2B亚基的小鼠（NR2B（δC/δC）小鼠）在围产期死亡。NR2A（δC/δC）小鼠是存活的，但表现出突触可塑性受损和情景记忆受损。这些小鼠以及NR2C（δC/δC）小鼠表现出运动协调缺陷。NR2亚基的C末端截短并不干扰可被突触激活的可门控受体通道的形成。因此，我们突变体的表型似乎反映了细胞内信号传导缺陷。
