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Genetic dissection identifies Necdin as a driver gene in a mouse model of paternal 15q duplications.
Tamada, Kota; Fukumoto, Keita; Toya, Tsuyoshi; Nakai, Nobuhiro; Awasthi, Janak R; Tanaka, Shinji; Okabe, Shigeo; Spitz, François; Saitow, Fumihito; Suzuki, Hidenori; Takumi, Toru.
Afiliación
  • Tamada K; RIKEN Brain Science Institute, Wako, Saitama, Japan.
  • Fukumoto K; Graduate School of Biomedical Sciences, Hiroshima University, Minami, Hiroshima, Japan.
  • Toya T; Department of Physiology and Cell Biology, Kobe University School of Medicine, Chuo, Kobe, Japan.
  • Nakai N; RIKEN Brain Science Institute, Wako, Saitama, Japan.
  • Awasthi JR; Graduate School of Biomedical Sciences, Hiroshima University, Minami, Hiroshima, Japan.
  • Tanaka S; RIKEN Brain Science Institute, Wako, Saitama, Japan.
  • Okabe S; Graduate School of Pharmaceutical Sciences, Keio University, Minato, Tokyo, Japan.
  • Spitz F; RIKEN Brain Science Institute, Wako, Saitama, Japan.
  • Saitow F; Graduate School of Biomedical Sciences, Hiroshima University, Minami, Hiroshima, Japan.
  • Suzuki H; Department of Physiology and Cell Biology, Kobe University School of Medicine, Chuo, Kobe, Japan.
  • Takumi T; RIKEN Brain Science Institute, Wako, Saitama, Japan.
Nat Commun ; 12(1): 4056, 2021 07 01.
Article en En | MEDLINE | ID: mdl-34210967
Maternally inherited duplication of chromosome 15q11-q13 (Dup15q) is a pathogenic copy number variation (CNV) associated with autism spectrum disorder (ASD). Recently, paternally derived duplication has also been shown to contribute to the development of ASD. The molecular mechanism underlying paternal Dup15q remains unclear. Here, we conduct genetic and overexpression-based screening and identify Necdin (Ndn) as a driver gene for paternal Dup15q resulting in the development of ASD-like phenotypes in mice. An excess amount of Ndn results in enhanced spine formation and density as well as hyperexcitability of cortical pyramidal neurons. We generate 15q dupΔNdn mice with a normalized copy number of Ndn by excising its one copy from Dup15q mice using a CRISPR-Cas9 system. 15q dupΔNdn mice do not show ASD-like phenotypes and show dendritic spine dynamics and cortical excitatory-inhibitory balance similar to wild type animals. Our study provides an insight into the role of Ndn in paternal 15q duplication and a mouse model of paternal Dup15q syndrome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trisomía / Conducta Animal / Proteínas Nucleares / Trastorno del Espectro Autista / Proteínas del Tejido Nervioso Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trisomía / Conducta Animal / Proteínas Nucleares / Trastorno del Espectro Autista / Proteínas del Tejido Nervioso Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido