Journal article

A Mutation in the Srrm4 Gene Causes Alternative Splicing Defects and Deafness in the Bronx Waltzer Mouse

Yoko Nakano, Israt Jahan, Gregory Bonde, Xingshen Sun, Michael S Hildebrand, John F Engelhardt, Richard JH Smith, Robert A Cornell, Bernd Fritzsch, Botond Banfi

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2012

Abstract

Sensory hair cells are essential for hearing and balance. Their development from epithelial precursors has been extensively characterized with respect to transcriptional regulation, but not in terms of posttranscriptional influences. Here we report on the identification and functional characterization of an alternative-splicing regulator whose inactivation is responsible for defective hair-cell development, deafness, and impaired balance in the spontaneous mutant Bronx waltzer (bv) mouse. We used positional cloning and transgenic rescue to locate the bv mutation to the splicing factor-encoding gene Ser/Arg repetitive matrix 4 (Srrm4). Transcriptome-wide analysis of pre-mRNA splicing in the s..

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University of Melbourne Researchers

Grants

Awarded by NIH


Awarded by March of Dimes Foundation


Awarded by University of Iowa Center for Gene Therapy for Cystic Fibrosis


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS


Funding Acknowledgements

This project was supported by grants from the NIH (R01DC010152 to BB, R01GM067841 to RAC, R01 DC005590 to BF), the March of Dimes Foundation (FY08-412 to RAC), and the University of Iowa Center for Gene Therapy for Cystic Fibrosis (NIH P30 DK-54759 to JFE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.