RNA expression profiling in brains of familial hemiplegic migraine type 1 knock-in mice.

Vries, Boukje de; Eising, Else; Broos, Ludo AM; Koelewijn, Stephany C; Todorov, Boyan; Frants, Rune R; Boer, Judith M; Ferrari, Michel D; Hoen, Peter AC ‘t; Maagdenberg, Arn MJM van den

Background: Various CACNA1A missense mutations cause familial hemiplegic migraine type 1 (FHM1), a rare monogenicsubtype of migraine with aura. FHM1 mutation R192Q is associated with pure hemiplegic migraine, whereas the S218Lmutation causes hemiplegic migraine, cerebellar ataxia, seizures, and mild head trauma-induced brain edema. Transgenicknock-in (KI) migraine mouse models were generated that carried either the FHM1 R192Q or the S218L mutation andwere shown to exhibit increased CaV2.1 channel activity. Here we investigated their cerebellar and caudal corticaltranscriptome.Methods: Caudal cortical and cerebellar RNA expression profiles from mutant and wild-type mice were studied usingmicroarrays. Respective brain regions were selected based on their relevance to migraine aura and ataxia. Relevantexpression changes were further investigated at RNA and protein level by quantitative polymerase chain reaction (qPCR)and/or immunohistochemistry, respectively.Results: Expression differences in the cerebellum were most pronounced in S218L mice. Particularly, tyrosine hydroxylase,a marker of delayed cerebellar maturation, appeared strongly upregulated in S218L cerebella. In contrast, onlyminimal expression differences were observed in the caudal cortex of either mutant mice strain.Conclusion: Despite pronounced consequences of migraine gene mutations at the neurobiological level, changes in corticalRNA expression in FHM1 migraine mice compared to wild-type are modest. In contrast, pronounced RNA expressionchanges are seen in the cerebellum of S218L mice and may explain their cerebellar ataxia phenotype.

GENETIC mutation; MIGRAINE; HEMIPLEGICS; MIGRAINE aura; GENE expression; LABORATORY mice

Cephalalgia, 2014, Vol 34, Issue 3, p174

0333-1024

Academic Journal

10.1177/0333102413502736