Your browser doesn't support javascript.
loading
Altered spinogenesis in iPSC-derived cortical neurons from patients with autism carrying de novo SHANK3 mutations.
Gouder, Laura; Vitrac, Aline; Goubran-Botros, Hany; Danckaert, Anne; Tinevez, Jean-Yves; André-Leroux, Gwenaëlle; Atanasova, Ekaterina; Lemière, Nathalie; Biton, Anne; Leblond, Claire S; Poulet, Aurélie; Boland, Anne; Deleuze, Jean-François; Benchoua, Alexandra; Delorme, Richard; Bourgeron, Thomas; Cloëz-Tayarani, Isabelle.
Afiliación
  • Gouder L; Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France.
  • Vitrac A; CNRS UMR 3571 « Genes, Synapses and Cognition ¼, Institut Pasteur, Paris, France.
  • Goubran-Botros H; Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
  • Danckaert A; Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France.
  • Tinevez JY; CNRS UMR 3571 « Genes, Synapses and Cognition ¼, Institut Pasteur, Paris, France.
  • André-Leroux G; Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
  • Atanasova E; Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France.
  • Lemière N; CNRS UMR 3571 « Genes, Synapses and Cognition ¼, Institut Pasteur, Paris, France.
  • Biton A; Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
  • Leblond CS; Imagopole, Citech, Institut Pasteur, Paris, France.
  • Poulet A; Imagopole, Citech, Institut Pasteur, Paris, France.
  • Boland A; MaIAGE, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
  • Deleuze JF; Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France.
  • Benchoua A; CNRS UMR 3571 « Genes, Synapses and Cognition ¼, Institut Pasteur, Paris, France.
  • Delorme R; Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
  • Bourgeron T; Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France.
  • Cloëz-Tayarani I; CNRS UMR 3571 « Genes, Synapses and Cognition ¼, Institut Pasteur, Paris, France.
Sci Rep ; 9(1): 94, 2019 01 14.
Article en En | MEDLINE | ID: mdl-30643170
The synaptic protein SHANK3 encodes a multidomain scaffold protein expressed at the postsynaptic density of neuronal excitatory synapses. We previously identified de novo SHANK3 mutations in patients with autism spectrum disorders (ASD) and showed that SHANK3 represents one of the major genes for ASD. Here, we analyzed the pyramidal cortical neurons derived from induced pluripotent stem cells from four patients with ASD carrying SHANK3 de novo truncating mutations. At 40-45 days after the differentiation of neural stem cells, dendritic spines from pyramidal neurons presented variable morphologies: filopodia, thin, stubby and muschroom, as measured in 3D using GFP labeling and immunofluorescence. As compared to three controls, we observed a significant decrease in SHANK3 mRNA levels (less than 50% of controls) in correlation with a significant reduction in dendritic spine densities and whole spine and spine head volumes. These results, obtained through the analysis of de novo SHANK3 mutations in the patients' genomic background, provide further support for the presence of synaptic abnormalities in a subset of patients with ASD.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Autístico / Células Piramidales / Mutación / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Autístico / Células Piramidales / Mutación / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido