家族性偏瘫型偏头痛（FHM）是常染色体显性遗传病，是研究偏头痛理想的疾病模型。本课题组已发现一个家系携带两个新的FHM基因突变位点ATP1A2（R279Q）、SCN1A（F1763V）。为明确二者及其编码离子通道结构功能的变化，探索不同类型神经细胞参与偏头痛的发生机制，建立并培育自主细胞及动物疾病模型，拟进行如下试验：将每个突变位点单独导入工具细胞或条件性敲入Cre小鼠中评价其生理功能变化和致病性；利用诱导多潜能干细胞技术培养患者来源的特异性细胞模型，并培育某一新突变的全身型基因敲入小鼠，再将另一新突变定向导入该小鼠脑中，以观察两个基因突变和其所在的神经细胞相互作用的致痛机制。通过上述方法建立更符合偏头痛特征的细胞和动物模型，深入探索偏头痛发病机制，为研发新的疾病干预措施提供有力工具。

Migraine is a high prevalent, disabling and undertreated episodic brain disorder, of which the mechanism remains unclear. Familial hemiplegic migraine (FHM) is a monogenic migraine syndrome with autosomal dominant inheritance, which is a potent tool for migraine research. We found a FHM family with two novel missense mutations. In order to clarify the function of these two novel mutations and explore the roles of different neuronal cells and ion channels involving in the migraine, and culture special cellular or animal models of migraine, we are going to do the systematic researches from bedside to the bench. First, transient transfect the different cell lines with the mutation vectors to observe the changes of cellular viability and electrophysiology. Second, predict the variation of the coded protein structures by the structural bioinformatics software. Third, generate induced pluripotent stem cells (iPSCs) from familial members and normal controls and differentiate iPSCs into neural cells, to set a kind of patient specific cellular disease model. Then, develop two strains of transgenic mice with two novel variants, using the Cre/loxP techniques. Based on these two strains of transgenic mice, give stimuli on the dura matter of the superior sagittal sinus, and detect the pathophysiological changes both in vitro and in vivo. And then, inject viral vectors with one mutant gene stereotaxicly into the brain of a strain of transgenic mice which carry the other mutant gene.These findings might open up new avenues for improved migraine prophylactic treatments and might also further the understanding of the pathology of migraine and migraine-comorbid disorders.