大学共同利用機関法人 自然科学研究機構

基礎生物学研究所

English

国際連携

国際共同研究成果 - 成果報告

Mutations in prickle orthologs cause seizures in flies, mice, and humans.

Authors Tao H, Manak JR, Sowers L, Mei X, Kiyonari H, Abe T, Dahdaleh NS, Yang T, Wu S, Chen S, Fox MH, Gurnett C, Montine T, Bird T, Shaffer LG, Rosenfeld JA, McConnell J, Madan-Khetarpal S, Berry-Kravis E, Griesbach H, Saneto RP, Scott MP, Antic D, Reed J, Bola
Journal Am J Hum Genet. 2011 Feb 11;88(2):138-49.
Link PudMed (http://www.ncbi.nlm.nih.gov/pubmed/21276947)

基礎生物学研究所形態形成部門とUniversity of Iowa, USAなどとの共同研究成果です。

Abstract

Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution.

最近の国際共同研究成果