McCall M A, Gregg R G, Behringer R R, Brenner M, Delaney C L, Galbreath E J, Zhang C L, Pearce R A, Chiu S Y, Messing A
Department of Pathobiological Sciences, University of Wisconsin-Madison, 53706, USA.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6361-6. doi: 10.1073/pnas.93.13.6361.
Glial fibrillary acidic protein (GFAP) is a member of the family of intermediate filament structural proteins and is found predominantly in astrocytes of the central nervous system (CNS). To assess the function of GFAP, we created GFAP-null mice using gene targeting in embryonic stem cells. The GFAP-null mice have normal development and fertility, and show no gross alterations in behavior or CNS morphology. Astrocytes are present in the CNS of the mutant mice, but contain a severely reduced number of intermediate filaments. Since astrocyte processes contact synapses and may modulate synaptic function, we examined whether the GFAP-null mice were altered in long-term potentiation in the CA1 region of the hippocampus. The GFAP-null mice displayed enhanced long-term potentiation of both population spike amplitude and excitatory post-synaptic potential slope compared to control mice. These data suggest that GFAP is important for astrocyte-neuronal interactions, and that astrocyte processes play a vital role in modulating synaptic efficacy in the CNS. These mice therefore represent a direct demonstration that a primary defect in astrocytes influences neuronal physiology.
胶质纤维酸性蛋白（GFAP）是中间丝结构蛋白家族的成员，主要存在于中枢神经系统（CNS）的星形胶质细胞中。为了评估GFAP的功能，我们利用胚胎干细胞基因靶向技术培育出了GFAP基因缺失的小鼠。GFAP基因缺失的小鼠发育和生育能力正常，行为或中枢神经系统形态也没有明显改变。突变小鼠的中枢神经系统中存在星形胶质细胞，但中间丝的数量严重减少。由于星形胶质细胞的突起与突触接触并可能调节突触功能，我们研究了GFAP基因缺失的小鼠在海马体CA1区的长时程增强是否发生改变。与对照小鼠相比，GFAP基因缺失的小鼠在群体峰电位幅度和兴奋性突触后电位斜率方面均表现出增强的长时程增强。这些数据表明，GFAP对星形胶质细胞与神经元的相互作用很重要，并且星形胶质细胞的突起在调节中枢神经系统的突触效能中起着至关重要的作用。因此，这些小鼠直接证明了星形胶质细胞的原发性缺陷会影响神经元生理功能。
