• Home
  • Search Results
  • Altered microtubule dynamics and vesicular transport in mouse and human MeCP2-deficient astrocytes.

Altered microtubule dynamics and vesicular transport in mouse and human MeCP2-deficient astrocytes.

Human molecular genetics (2015-11-26)
Chloé Delépine, Hamid Meziane, Juliette Nectoux, Matthieu Opitz, Amos B Smith, Carlo Ballatore, Yoann Saillour, Annelise Bennaceur-Griscelli, Qiang Chang, Emily Cunningham Williams, Maxime Dahan, Aurélien Duboin, Pierre Billuart, Yann Herault, Thierry Bienvenu

Rett syndrome (RTT) is a rare X-linked neurodevelopmental disorder, characterized by normal post-natal development followed by a sudden deceleration in brain growth with progressive loss of acquired motor and language skills, stereotypic hand movements and severe cognitive impairment. Mutations in the methyl-CpG-binding protein 2 (MECP2) cause more than 95% of classic cases. Recently, it has been shown that the loss of Mecp2 from glia negatively influences neurons in a non-cell-autonomous fashion, and that in Mecp2-null mice, re-expression of Mecp2 preferentially in astrocytes significantly improved locomotion and anxiety levels, restored respiratory abnormalities to a normal pattern and greatly prolonged lifespan compared with globally null mice. We now report that microtubule (MT)-dependent vesicle transport is altered in Mecp2-deficient astrocytes from newborn Mecp2-deficient mice compared with control wild-type littermates. Similar observation has been made in human MECP2 p.Arg294* iPSC-derived astrocytes. Importantly, administration of Epothilone D, a brain-penetrant MT-stabilizing natural product, was found to restore MT dynamics in Mecp2-deficient astrocytes and in MECP2 p.Arg294* iPSC-derived astrocytes in vitro. Finally, we report that relatively low weekly doses of Epothilone D also partially reversed the impaired exploratory behavior in Mecp2(308/y) male mice. These findings represent a first step toward the validation of an innovative treatment for RTT.

Product Number
Product Description

Fibronectin bovine plasma, solution, sterile-filtered, BioReagent, suitable for cell culture
Monoclonal Anti-α-Tubulin antibody produced in mouse, clone DM1A, ascites fluid
Monoclonal Anti-Tubulin, Acetylated antibody produced in mouse, clone 6-11B-1, ascites fluid
Monoclonal Anti-S-100 (β-Subunit) antibody produced in mouse, clone SH-B1, ascites fluid