抑郁症是严重威胁人类健康的精神类疾病，全球发病率约16%。其发生发展受环境因素和遗传因素的双重影响。但对抑郁症的致病机理以及其遗传突变目前尚不清楚。MEN1基因是多发性内分泌肿瘤1型综合征的致病基因，也是众所周知的抑癌基因。多项研究表明，menin在神经系统中作用极为重要。我们在1000多例重症抑郁患者以及500多例对照者的基因测序中发现，menin和抑郁症的发生发展有密切的联系，我们还从中发现了MEN1的一个SNP（rs375804228，menin G503D）与抑郁显著相关。因此我们通过转基因小鼠条件性敲除Men1，研究menin的缺失对抑郁症发生的作用机制。我们的科学假设是menin在星形胶质细胞中的缺失导致了NF-κB的激活，进而造成了下游炎症因子的释放，从而导致抑郁的发生。本研究旨在阐明menin在抑郁中的作用，并为抑郁的早期诊断，治疗和判断预后提供可能的依据。

Major Depression Disorder (MDD) is one of the most important psychiatric disorders leads to morbidity and mortality. Although the dysfunction of astrocyte and the activation of the inflammatory process are highly involved in this disorder, the underlying mechanism remains largely unknown. We found that deletion of tumor suppressor menin (Men1) in astrocyte but not in neuron was involved in the development of MDD in mice, characterized by depressed mood, social interactivity deficit. Furthermore, the levels of proinflammatory factors including IL-1beta were dramatically increased in Men1-astrocyte deficient mice due to abnormally activation of NF-kappa B. We try to identify that menin associated with NF-kappa B subunit P65 and inhibited its DNA binding ability. We found a SNP in coding region of MEN1 have a higher risk of MDD, which promote the activation of NF-kappaB and IL-1beta generation. Our subject is to reveal a distinguished astroglial role of menin in regulating inflammation in depression, and targeting menin may be therapeutically beneficial.