Paylor R, Johnson R S, Papaioannou V, Spiegelman B M, Wehner J M
Institute for Behavioral Genetics, University of Colorado, Boulder 80309-0447.
Brain Res. 1994 Jul 18;651(1-2):275-82. doi: 10.1016/0006-8993(94)90707-2.
Induction of the proto-oncogene c-fos has been associated with a number of neural and behavioral responses to acute stimuli. Behavioral characterization of mice containing a mutant c-fos allele created via homologous recombination-based gene targeting was performed to analyze the role of this protein in baseline neurological properties as well as paradigms that require neural adaptive responses. Performance of 9 out of 11 c-fos-deficient animals was impaired in the spatial version of the Morris water task. However, this poor performance in the spatial version of the task was highly correlated to their performance in the non-spatial version of the task which suggests that they have a behavioral impairment that interrupts their ability to perform adequately on both versions of the task with the same proficiency as wild-type and heterozygous litter mates. To examine learning impairments further, a simple left/right discrimination in a T-maze was used. Mutants were not impaired in this simple learning task. These results suggest that c-fos mutants have some behavioral impairments that interfere with evaluation of complex learning on the Morris water task, but because all genotypes could perform a simple discrimination task, it is clear that c-fos is not essential for this simpler form of learning and memory.
原癌基因c-fos的诱导与对急性刺激的多种神经和行为反应有关。通过基于同源重组的基因靶向技术创建了含有突变c-fos等位基因的小鼠,并对其进行行为特征分析,以研究该蛋白在基线神经特性以及需要神经适应性反应的范式中的作用。在Morris水迷宫任务的空间版本中,11只c-fos缺陷动物中有9只的表现受损。然而,该任务空间版本中的这种不佳表现与其在非空间版本任务中的表现高度相关,这表明它们存在行为障碍,从而影响了它们以与野生型和杂合子同窝小鼠相同的熟练度在两个版本任务中充分表现的能力。为了进一步检查学习障碍,使用了T迷宫中的简单左右辨别任务。突变体在这个简单的学习任务中没有受损。这些结果表明,c-fos突变体存在一些行为障碍,干扰了对Morris水迷宫任务中复杂学习的评估,但由于所有基因型都能完成简单的辨别任务,显然c-fos对于这种较简单形式的学习和记忆并非必不可少。