School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.
Centre for MND Research, Macquarie University, Sydney, New South Wales, Australia.
Genes Brain Behav. 2021 Jun;20(5):e12735. doi: 10.1111/gbb.12735.
Environmental factors inherent to animal facilities can impact on the neuro-behavioural phenotype of laboratory mice and genetic mouse models for human diseases. Many facilities have upgraded from traditional 'open filter top' cages (FT) to individually ventilated cage (IVC) systems, which have been shown to modify various behavioural responses of laboratory mice. Importantly, the impact of IVC housing on the G93A superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis (ALS) is currently unknown. Male and female wild type-like (WT) and heterozygous SOD1 mice were group-housed in FT or IVC systems from PND 30 ± 5 onwards. Body weight and motor function were assessed weekly from 15 weeks onward. Mice were also tested for cognitive abilities (i.e., fear conditioning and social recognition memory) and sensorimotor gating (i.e., prepulse inhibition: PPI). SOD1 mice lost body weight, and their motor function degenerated over time compared with control littermates. Motor impairments developed faster when SOD1 females were housed in IVCs. Context and cue freezing were increased in SOD1 females compared with controls, whereas all SOD1 mice exhibited lower acoustic startle and PPI than WT mice. IVC housing led to an increase in cue freezing in males and reduced the severity of PPI deficits in SOD1 females. Overall, IVC housing impacted moderately on the SOD1 phenotype but central behavioural deficits were still evident across housing conditions. Nonetheless, our findings indicate the importance of assessing the effect of cage system in genetic mouse models as these systems can modulate the magnitude and onset of genotypic differences.
动物设施固有的环境因素会影响实验小鼠的神经行为表型和人类疾病的遗传小鼠模型。许多设施已经从传统的“开放式过滤顶笼（FT）”升级到了单独通风笼（IVC）系统，事实证明，这种系统可以改变实验小鼠的各种行为反应。重要的是，目前尚不清楚 IVC 饲养对肌萎缩侧索硬化症（ALS）的 G93A 超氧化物歧化酶 1 小鼠模型的影响。从 PND30±5 开始，雄性和雌性野生型（WT）和杂合 SOD1 小鼠被分组饲养在 FT 或 IVC 系统中。从 15 周龄开始，每周评估体重和运动功能。还对小鼠进行了认知能力（即恐惧条件反射和社交识别记忆）和感觉运动门控（即预脉冲抑制：PPI）测试。与对照同窝仔相比，SOD1 小鼠的体重减轻，运动功能随时间退化。当 SOD1 雌性被饲养在 IVC 中时，运动损伤发展得更快。与对照组相比，SOD1 雌性的上下文和线索冻结增加，而所有 SOD1 小鼠的听觉起始和 PPI 都低于 WT 小鼠。IVC 饲养导致雄性线索冻结增加，并减少了 SOD1 雌性 PPI 缺陷的严重程度。总体而言，IVC 饲养对 SOD1 表型有一定影响，但在不同的饲养条件下仍然存在中枢行为缺陷。尽管如此，我们的研究结果表明，在遗传小鼠模型中评估笼系统的效果非常重要，因为这些系统可以调节基因型差异的程度和出现。
