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Behavioural effects of cage systems on the G93A Superoxide Dismutase 1 transgenic mouse model for amyotrophic lateral sclerosis
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2021-04-19 , DOI: 10.1111/gbb.12735 Stefan Guerra 1 , Roger Chung 2 , Justin Yerbury 3 , Tim Karl 1, 4
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2021-04-19 , DOI: 10.1111/gbb.12735 Stefan Guerra 1 , Roger Chung 2 , Justin Yerbury 3 , Tim Karl 1, 4
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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 SOD1G93A 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). SOD1G93A mice lost body weight, and their motor function degenerated over time compared with control littermates. Motor impairments developed faster when SOD1G93A females were housed in IVCs. Context and cue freezing were increased in SOD1G93A females compared with controls, whereas all SOD1G93A 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 SOD1G93A females. Overall, IVC housing impacted moderately on the SOD1G93A 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.
中文翻译：
笼子系统对肌萎缩侧索硬化 G93A 超氧化物歧化酶 1 转基因小鼠模型的行为影响
动物设施固有的环境因素会影响实验室小鼠的神经行为表型和人类疾病的遗传小鼠模型。许多设施已从传统的“开放式过滤器顶部”笼 (FT) 升级到单独通风笼 (IVC) 系统，这些系统已被证明可以改变实验室小鼠的各种行为反应。重要的是，IVC 外壳对肌萎缩侧索硬化 (ALS) 的G93A 超氧化物歧化酶 1小鼠模型的影响目前尚不清楚。雄性和雌性野生型样 (WT) 和杂合SOD1 G93A从 PND 30 ± 5 起，小鼠被分组饲养在 FT 或 IVC 系统中。从 15 周起每周评估体重和运动功能。还测试了小鼠的认知能力（即恐惧条件反射和社会识别记忆）和感觉运动门控（即前脉冲抑制：PPI）。与对照同窝小鼠相比， SOD1 G93A小鼠体重减轻，运动功能随着时间的推移而退化。当SOD1 G93A女性被安置在 IVC 中时，运动障碍发展得更快。与对照组相比，SOD1 G93A女性的语境和提示冻结增加，而所有SOD1 G93A小鼠表现出比 WT 小鼠更低的听觉惊吓和 PPI。IVC 住房导致男性的提示冻结增加，并降低了SOD1 G93A女性 PPI 缺陷的严重程度。总体而言，IVC 住房对SOD1 G93A表型有适度影响，但在住房条件下，中心行为缺陷仍然很明显。尽管如此，我们的研究结果表明评估笼子系统在遗传小鼠模型中的影响的重要性，因为这些系统可以调节基因型差异的大小和开始。
更新日期：2021-06-05
中文翻译：
笼子系统对肌萎缩侧索硬化 G93A 超氧化物歧化酶 1 转基因小鼠模型的行为影响
动物设施固有的环境因素会影响实验室小鼠的神经行为表型和人类疾病的遗传小鼠模型。许多设施已从传统的“开放式过滤器顶部”笼 (FT) 升级到单独通风笼 (IVC) 系统，这些系统已被证明可以改变实验室小鼠的各种行为反应。重要的是，IVC 外壳对肌萎缩侧索硬化 (ALS) 的G93A 超氧化物歧化酶 1小鼠模型的影响目前尚不清楚。雄性和雌性野生型样 (WT) 和杂合SOD1 G93A从 PND 30 ± 5 起，小鼠被分组饲养在 FT 或 IVC 系统中。从 15 周起每周评估体重和运动功能。还测试了小鼠的认知能力（即恐惧条件反射和社会识别记忆）和感觉运动门控（即前脉冲抑制：PPI）。与对照同窝小鼠相比， SOD1 G93A小鼠体重减轻，运动功能随着时间的推移而退化。当SOD1 G93A女性被安置在 IVC 中时，运动障碍发展得更快。与对照组相比，SOD1 G93A女性的语境和提示冻结增加，而所有SOD1 G93A小鼠表现出比 WT 小鼠更低的听觉惊吓和 PPI。IVC 住房导致男性的提示冻结增加，并降低了SOD1 G93A女性 PPI 缺陷的严重程度。总体而言，IVC 住房对SOD1 G93A表型有适度影响，但在住房条件下，中心行为缺陷仍然很明显。尽管如此，我们的研究结果表明评估笼子系统在遗传小鼠模型中的影响的重要性，因为这些系统可以调节基因型差异的大小和开始。
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