Montkowski A, Poettig M, Mederer A, Holsboer F
Max Planck Institute of Psychiatry, Clinical Institute, Department of Neuroendocrinology, Munich, Germany.
Brain Res. 1997 Jul 11;762(1-2):12-8. doi: 10.1016/s0006-8993(97)00370-3.
Recently, the possibility has been raised that the behavioural abnormalities seen in null-mutant mice might be determined by their genetic background rather than by loss of gene function, especially when the 129 mouse strain is used as supplier for embryonic stem (ES) cells. To examine this issue we tested three 129 mouse substrains (129/J, 129/Ola, 129/Sv-ter/+) and C57BL/6 (B6) in the Morris water maze, the open field, the plus maze and two tests assessing motor co-ordination. We identified only for the 129/J substrain substantial behavioural deficits. These mice are albinos and carry the pink-eyed dilution allele and differed in their basal anxiety level as assessed in the open-field test. They were severely impaired in spatial learning and memory (Morris water maze test), in the Porsolt swim test, which also measures learning and in motor co-ordination. However, the 129/J substrain has not been used as ES cell donor in null-mutant mice where behavioural abnormalities were observed. Instead, mice from 129/Ola and 129/Sv-ter/+ substrains have been commonly used as suppliers for ES cells. These performed normally in most of the tests, including Morris water maze test.
最近,有人提出在基因敲除小鼠中观察到的行为异常可能由其遗传背景决定,而非基因功能丧失所致,尤其是当使用129小鼠品系作为胚胎干细胞(ES细胞)的供体时。为了研究这个问题,我们在莫里斯水迷宫、旷场试验、十字迷宫以及两项评估运动协调性的试验中,对三种129小鼠亚系(129/J、129/Ola、129/Sv-ter/+)和C57BL/6(B6)小鼠进行了测试。我们仅在129/J亚系中发现了显著的行为缺陷。这些小鼠是白化病小鼠,携带粉红眼稀释等位基因,在旷场试验中评估的基础焦虑水平有所不同。它们在空间学习和记忆(莫里斯水迷宫试验)、也用于测量学习能力的波索尔特游泳试验以及运动协调性方面均严重受损。然而,在观察到行为异常的基因敲除小鼠中,尚未使用129/J亚系作为ES细胞供体。相反,129/Ola和129/Sv-ter/+亚系的小鼠通常被用作ES细胞的供体。这些小鼠在大多数试验中表现正常,包括莫里斯水迷宫试验。