Casein kinase iδ mutations in familial migraine and advanced sleep phase.

TitleCasein kinase iδ mutations in familial migraine and advanced sleep phase.
Publication TypeJournal Article
Year of Publication2013
AuthorsBrennan KC, Bates EA, Shapiro RE, Zyuzin J, Hallows WC, Huang Y, Lee H-Y, Jones CR, Fu Y-H, Charles AC, Ptáček LJ
JournalScience translational medicine
Volume5
Issue183
Pagination183ra56, 1-11
Date Published2013 May 1
Abstract

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.

DOI10.1074/jbc.M113.506568
Alternate JournalSci Transl Med