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7个连续的父本表达基因缺失引发的多基因遗传病。此前全PWS基因失活的小鼠模型在出生后第一周内死亡率达100%，且未能为阐明该综合征的出生后病理生理机制提供助力。针对每个候选基因的敲除（Knockout, KO）模型也已构建，但此类模型无法体现PWS相关基因间的功能互作与潜在代偿功能。本研究构建了一种新型双基因敲除（double KO）小鼠模型，以探究Magel2与Necdin联合缺失的生物学效应。实验设计概述：小鼠饲养于标准动物房环境，自由采食饮水，采用12小时光照/12小时黑暗的光周期（LD）饲养。分别在光照开启后6小时（昼组）与光照开启后18小时（夜组）处死C57BL/6J野生型（WT）小鼠与双敲除MADIN小鼠，随后提取总RNA进行测序（total RNA sequencing）。