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Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia.

Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. Research Abstract Details 

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  • Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. Abstract Text:

    wei tanWei Tan,yanhong wangYanhong Wang,bert goldBert Gold,jingshan chenJingshan Chen,michael deanMichael Dean,paul j harrisonPaul J Harrison,daniel r weinbergerDaniel R Weinberger,amanda j lawAmanda J Law,

    Neuregulin 1 (NRG1) is essential for the development and function of multiple organ systems, and its dysregulation has been linked to diseases such as cancer and schizophrenia. Recently, altered expression of a novel isoform (type IV) in the brain has been associated with schizophrenia-related genetic variants, especially rs6994992 (SNP8NRG243177). Here we have isolated and characterized full-length NRG1 type IV cDNAs from the adult and fetal human brain and identified novel splice variants of NRG1. Full-length type IV spans 1.8 kb and encodes a putative protein of 590 amino acids with a predicted molecular mass of approximately 66 kDa. The transcript consists of 11 exons with an Ig-like domain, an epidermal growth factor-like (EGF) domain, a beta-stalk, a transmembrane domain, and a cytoplasmic "a-tail," placing it in the beta1a NRG1 subclass. NRG1 type IV was not detected in any tissues except brain and a putative type IV NRG1 protein of 66 kDa was similarly brain-specific. Type IV transcripts are more abundantly expressed in the fetal brain, where, in addition to the full-length structure, two novel type IV variants were identified. In vitro luciferase-reporter assays demonstrate that the 5' promoter region upstream of type IV is functional, with differential activity associated with genetic variation at rs6994992, and that promoter competition may impact on type IV expression. Our data suggest that type IV is a unique brain-specific NRG1 that is differentially expressed and processed during early development, is translated, and its expression regulated by a schizophrenia risk-associated functional promoter or single nucleotide polymorphism (SNP).

    Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. Publishing Authors By Initials

    w tanW Tan,y wangY Wang,b goldB Gold,j chenJ Chen,m deanM Dean,pj harrisonPJ Harrison,dr weinbergerDR Weinberger,aj lawAJ Law,

    For similar mental disorders: schizophrenia and disorders with psychotic features: schizophrenia research abstracts see: mental disorders: schizophrenia and disorders with psychotic features: schizophrenia research

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    Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: The Journal of biological chemistry

    VOLUME: 282

    Page Numbers: 24343-51

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 12

    MONTH: 06

    YEAR: 2007

    Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985121

    Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. Keywords Mesh Terms:

    KEYWORDS: Schizophrenia

    MESH TERMS: genetics

    Chemical & Substance for Abstract: Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. Information

    Substance Name: Protein Isoforms

    Registry Number: 0

    Grant and Affiliation Information for Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia.

    AFFILIATION: SAIC-Frederick, NCI, National Institutes of Health, Frederick, Maryland 21702, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCI

    GRANT: N01-CO-12400

    ACRONYM: CO

    MEDLINETA: J Biol Chem

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