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Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology.

Lori A Orosco | Adam P Ross | Staci L Cates | Sean E Scott | Dennis Wu | Jiho Sohn | David Pleasure | Samuel J Pleasure | Iannis E Adamopoulos | Konstantinos S Zarbalis
Nature communications | 2014

Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs.

Pubmed ID: 25198012

Associated grants

  • Agency: NCRR NIH HHS, United States
    Id: U42 RR024244
  • Agency: NHGRI NIH HHS, United States
    Id: U01HG004085
  • Agency: NICHD NIH HHS, United States
    Id: R21 HD067855
  • Agency: PHS HHS, United States
    Id: NICHD R21HD67855
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG004080
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH105360
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG004085
  • Agency: NCRR NIH HHS, United States
    Id: U42RR024244
  • Agency: NHGRI NIH HHS, United States
    Id: U01HG004080

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Knockout Mouse Project Repository (tool)

RRID:SCR_007318

Repository of mouse vectors, ES cells, mice, embryos, and sperm generated by NIH KOMP Mutagenesis Project. In addition, KOMP Repository offers services in support of KOMP products, including ES cell microinjection, vector cloning, post-insertional modification of cloned ES cells, cryopreservation, assisted reproduction techniques (IVF, ICSI) and mouse breeding, pathology services, phenotyping services, etc. KOMP Repository is final component of more than $50 million trans-NIH initiative to increase availability of genetically altered mice and related materials. The University of California, Davis (UC Davis) and Children''s Hospital Oakland Research Institute (CHORI) in Oakland, Calif., are collaborating to preserve, protect, and make available about 8,500 types of knockout mice and related products available to research community. Products are generated by two KOMP mutagenesis teams (CSD consortium and Regeneron Inc). All KOMP products generated by CSD consortium and Regeneron are available through KOMP Repository. Notice as of December 19, 2019: Materials from KOMP Repository have been deposited into MMRRC, including all mouse models and mouse embryonic stem cell lines. Eventually www.komp.org will be sunsetting, and IMSR will remove KOMP Repository listings, since they were double listed in MMRRC. MMRRC will contain the most accurate and up to date resource models.

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RRID:SCR_001247

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RRID:MGI:2159965

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