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J. Biol. Chem., Vol. 282, Issue 33, 99933, August 17, 2007

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Insight into a Schizophrenia-related Mutation

Neuregulin 1 (NRG1) is a signaling protein that mediates cell-cell interactions and plays critical roles in the growth of the nervous system, heart, breast, and other organ systems. The protein is produced in numerous isoforms by alternative splicing, which allows it to perform a wide variety of functions. Recently, the altered expression of the type IV isoforms, especially the rs6994992 variant, has been linked to a risk for schizophrenia (1).

NRG1 is expressed only in the adult and fetal brain.

In this Paper of the Week, Wei Tan and colleagues provide insight into the biology and structure of the full-length NRG1 type IV. They show that NRG1 type IV mRNA and protein are expressed only in the brain and that they are more abundant in the fetal brain, which also contains several novel type IV splice variants. Tan et al. also isolated and characterized part of the type IV promoter and showed that there are allelic-specific differences in rs6994992 promoter activity and promoter competition with a neighboring NRG1 promoter. These data indicate that the schizophrenia risk-associated rs6994992 is a functional promoter variant associated with schizophrenia genetic predisposition and NRG1 type IV expression.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 24343-24351

REFERENCES

1. Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T. T. et al. (2002) Neuregulin 1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892[CrossRef][Medline] [Order article via Infotrieve]

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This Article Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Papers Of The Week Social Bookmarking                      What's this?