Proteomics, bioinformatics and targeted gene expression analysis reveals up-regulation of cochlin and identifies other potential biomarkers in the mouse model for deafness in Usher syndrome type 1F.

Human Molecular Genetics
Mark R ChanceKumar Alagramam

Abstract

Proteins and protein networks associated with cochlear pathogenesis in the Ames waltzer (av) mouse, a model for deafness in Usher syndrome 1F (USH1F), were identified. Cochlear protein from wild-type and av mice at postnatal day 30, a time point in which cochlear pathology is well established, was analyzed by quantitative 2D gel electrophoresis followed by mass spectrometry (MS). The analytic gel resolved 2270 spots; 69 spots showed significant changes in intensity in the av cochlea compared with the control. The cochlin protein was identified in 20 peptide spots, most of which were up-regulated, while a few were down-regulated. Analysis of MS sequence data showed that, in the av cochlea, a set of full-length isoforms of cochlin was up-regulated, while isoforms missing the N-terminal FCH/LCCL domain were down-regulated. Protein interaction network analysis of all differentially expressed proteins was performed with Metacore software. That analysis revealed a number of statistically significant candidate protein networks predicted to be altered in the affected cochlea. Quantitative PCR (qPCR) analysis of select candidates from the proteomic and bioinformatic investigations showed up-regulation of Coch mRNA and those of p53, Brn3...Continue Reading

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Citations

Sep 21, 2012·Cell and Tissue Research·Audrey P CalzadaGail Ishiyama
Nov 19, 2013·PloS One·Adrian AuKumar Alagramam
Nov 21, 2014·Bioanalysis·Szymon FilipHarald Mischak
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Mar 1, 2012·PloS One·Marisa ZallocchiDominic Cosgrove
Mar 22, 2015·Expert Review of Proteomics·Ali AlawiehMarc Bassim

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