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Behavioral abnormalities and circuit defects in the basal ganglia of a mouse model of 16p11.2 deletion syndrome.
Portmann, Thomas; Yang, Mu; Mao, Rong; Panagiotakos, Georgia; Ellegood, Jacob; Dolen, Gul; Bader, Patrick L; Grueter, Brad A; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Kalikhman, David; Loureiro, Darren; Saw, Nay L; Zhengqui, Zhou; Miller, Michael A; Lerch, Jason P; Henkelman, Mark; Shamloo, Mehrdad; Malenka, Robert C; Crawley, Jacqueline N; Dolmetsch, Ricardo E.
Afiliação
  • Portmann T; Department of Neurobiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Yang M; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Mao R; Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD 20892-9663, USA.
  • Panagiotakos G; Department of Neurobiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Ellegood J; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Dolen G; Department of Neurobiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Bader PL; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Grueter BA; Neurosciences Program, Stanford University, Stanford, CA 94305-5345, USA.
  • Goold C; Mouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, ON M5T 3H7, Canada.
  • Fisher E; Department of Neuroscience, Brain Science Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Clifford K; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Rengarajan P; Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Kalikhman D; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Loureiro D; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305-5345, USA.
  • Saw NL; Department of Neurobiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Zhengqui Z; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Miller MA; Department of Neurobiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Lerch JP; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Henkelman M; Department of Neurobiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Shamloo M; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Malenka RC; Department of Neurobiology, Stanford University, Stanford, CA 94305-5345, USA.
  • Crawley JN; School of Medicine, Stanford University, Stanford, CA 94305-5345, USA.
  • Dolmetsch RE; Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD 20892-9663, USA.
Cell Rep ; 7(4): 1077-1092, 2014 May 22.
Article em En | MEDLINE | ID: mdl-24794428
ABSTRACT
A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Gânglios da Base / Deleção Cromossômica / Transtornos Cromossômicos / Modelos Animais de Doenças / Transtornos Mentais / Deficiência Intelectual Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Gânglios da Base / Deleção Cromossômica / Transtornos Cromossômicos / Modelos Animais de Doenças / Transtornos Mentais / Deficiência Intelectual Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos