A novel mouse model of Prader-Willi Syndrome including the deletion of both Necdin and Magel2 genes. A novel mouse model of Prader-Willi Syndrome including the deletion of both Necdin and Magel2 genes

Prader-Willi syndrome (PWS) is a multigenic disorder caused by the loss of seven contiguous paternally expressed genes. Mouse models with inactivation of all PWS genes display 100% lethality within the first postnatal week and have not helped understand the postnatal pathophysiology of this syndrome. Knockout (KO) models for each candidate gene were also generated, but they lack the functional interactions and possible compensatory functions between PWS-related genes. Here, we generated a novel double KO mouse model to explore the effect of a combined deletion of Magel2 and Necdin. Overall design: Mice were maintained under standard animal housing conditions, with free access to food and water,, and in standard 12-h light/12-h dark cycles (LD). C57BL/6J mice (WT) and double ko mice (MADIN) were sacrificed either six hour after light on (the DAY group) or 18 hours after light on (the NIGHT group) and were processed for total RNA sequencing

普拉德-威利综合征（Prader-Willi syndrome, PWS）是一种由七个连续的父本表达基因缺失引发的多基因紊乱疾病。对所有PWS相关基因进行灭活的小鼠模型，在出生后第一周内全部死亡，且未能助力阐明该综合征的产后病理生理学机制。此外，研究人员还构建了各候选基因的敲除（Knockout, KO）模型，但这类模型无法体现PWS相关基因之间的功能互作与潜在代偿效应。本研究构建了一种新型双基因敲除小鼠模型，以探究Magel2与Necdin联合缺失的生物学效应。整体实验设计：实验小鼠饲养于标准动物房环境中，可自由获取食物与饮水，光照周期为标准的12小时光照/12小时黑暗（LD）。分别在光照开启后6小时（昼组）与光照开启后18小时（夜组），对C57BL/6J野生型（Wild Type, WT）小鼠与双基因敲除小鼠（MADIN）实施安乐死，随后开展总RNA测序。