Casein kinase iδ mutations in familial migraine and advanced sleep phase.
Casein kinase iδ mutations in familial migraine and advanced sleep phase.
复制标题
DOI：
10.1126/scitranslmed.3005784
复制
发表时间：
2013-05-01
影响因子：
17.1
通讯作者：
Ptáček LJ
中科院分区：
文献类型：
--
作者：
Brennan KC;Bates EA;Shapiro RE;Zyuzin J;Hallows WC;Huang Y;Lee HY;Jones CR;Fu YH;Charles AC;Ptáček LJ
偏头痛是一种常见的致残性疾病，具有显着的遗传因素，其特点是严重头痛，常伴有恶心、呕吐和光敏感。我们鉴定了两个家族，每个家族的酪蛋白激酶 Iδ (CKIδ) 编码基因均存在明显的错义突变，其中该突变与偏头痛和晚期睡眠阶段共分离。由此产生的改变（T44A 和 H46R）发生在 CKIδ 的保守催化结构域中，导致酶活性降低。携带 CKIδ-T44A 等位基因的小鼠在接受偏头痛触发硝酸甘油治疗后对疼痛更加敏感。 CKIδ-T44A 小鼠还表现出皮质扩散抑制阈值降低（被认为是偏头痛先兆的生理类似物）以及皮质扩散抑制期间更大的动脉扩张。 CKIδ-T44A 小鼠的星形胶质细胞显示出自发和诱发的钙信号传导增加。这些遗传、细胞、生理和行为分析表明，CKIδ 活性的降低可能导致偏头痛的发病机制。
Migraine is a common disabling disorder with a significant genetic component, characterized by severe headache and often accompanied by nausea, vomiting, and light sensitivity. We identified two families, each with a distinct missense mutation in the gene encoding casein kinase Iδ (CKIδ), in which the mutation cosegregated with both the presence of migraine and advanced sleep phase. The resulting alterations (T44A and H46R) occurred in the conserved catalytic domain of CKIδ, where they caused reduced enzyme activity. Mice engineered to carry the CKIδ-T44A allele were more sensitive to pain after treatment with the migraine trigger nitroglycerin. CKIδ-T44A mice also exhibited a reduced threshold for cortical spreading depression (believed to be the physiological analog of migraine aura) and greater arterial dilation during cortical spreading depression. Astrocytes from CKIδ-T44A mice showed increased spontaneous and evoked calcium signaling. These genetic, cellular, physiological, and behavioral analyses suggest that decreases in CKIδ activity can contribute to the pathogenesis of migraine.
登录
查看更多内容
影响因子：
11.2
作者：
Burstein, R;Collins, B;Jakubowski, M
通讯作者：
Jakubowski, M
影响因子：
30.8
作者：
De Fusco, M;Marconi, R;Casari, G
通讯作者：
Casari, G
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
14.5
作者：
Chang, Joshua C.;Shook, Lydia L.;Brennan, Kevin C.
通讯作者：
Brennan, Kevin C.
影响因子：
4.9
作者：
Christiansen, I;Thomsen, LL;Olesen, J
通讯作者：
Olesen, J