Derepression of a neuronal inhibitor due to miRNA dysregulation in a schizophrenia-related microdeletion

Bin Xu, Pei Ken Hsu, Kimberly L. Stark, Maria Karayiorgou*, Joseph A. Gogos

*Corresponding author for this work

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

22q11.2 microdeletions result in specific cognitive deficits and schizophrenia. Analysis of Df(16)A+/- mice, which model this microdeletion, revealed abnormalities in the formation of neuronal dendrites and spines, as well as altered brain microRNAs. Here, we show a drastic reduction of miR-185, which resides within the 22q11.2 locus, to levels more than expected by a hemizygous deletion, and we demonstrate that this reduction alters dendritic and spine development. miR-185 represses, through an evolutionarily conserved target site, a previously unknown inhibitor of these processes that resides in the Golgi apparatus and shows higher prenatal brain expression. Sustained derepression of this inhibitor after birth represents the most robust transcriptional disturbance in the brains of Df(16)A+/- mice and results in structural alterations in the hippocampus. Reduction of miR-185 also has milder age- and region-specific effects on the expression of some Golgi-related genes. Our findings illuminate the contribution of microRNAs in psychiatric disorders and cognitive dysfunction.

Original languageEnglish (US)
Pages (from-to)262-275
Number of pages14
JournalCell
Volume152
Issue number1-2
DOIs
StatePublished - Jan 7 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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