ジュベール症候群の子どもたちに見られる知的障害と、脳の特定部位の欠陥との間に重要な関連性があることが明らかに。 An important link has been found between the intellectual disability seen in children with Joubert Syndrome and defects in a specific part of the brain.
2022-05-10 バース大学
バース大学の生物学者であるVasanta Subramanian博士は、ヒトのJSの原因として知られている遺伝子(34のうちの1つ)を操作することにより、動物モデルでこの関連性を明らかにしました。この研究結果は、『Human Molecular Genetics』誌に掲載されています。
<関連情報>
- https://www.bath.ac.uk/announcements/joubert-syndrome-the-link-between-intellectual-disability-and-defects-in-the-hippocampus/
- https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddac095/6573777?login=false
Talpid3のコイルドコイル領域欠損マウスでは海馬のニューロン新生が阻害される-Joubert症候群への示唆 Hippocampal neurogenesis is impaired in mice with a deletion in the coiled coil domain of Talpid3—implications for Joubert syndrome
Andrew L Bashford, Vasanta Subramanian
Human Molecular Genetics Published:26 April 2022
DOI:https://doi.org/10.1093/hmg/ddac095
Abstract
Mutations in Talpid3, a basal body protein essential for the assembly of primary cilia have been reported to be causative for Joubert Syndrome. Herein, we report prominent developmental defects in the hippocampus of a conditional knockout mouse lacking the conserved exons 11 and 12 of Talpid3. At early postnatal stages, the Talpid3 mutants exhibit a reduction in proliferation in the dentate gyrus and a disrupted glial scaffold. The occurrence of mis-localised progenitors in the GCL suggests a role for the disrupted glial scaffold in cell migration resulting in defective SPZ-to-hilar transition. Neurospheres derived from the hippocampus of Talpid3fl/flUbcCre mouse in which Talpid3 was conditionally deleted, lacked primary cilia and were smaller in size. In addition, neurosphere cells showed a disrupted actin cytoskeleton and defective migration. Our findings suggest a link between the hippocampal defects and the learning/memory deficits seen in JS patients.
