Gene expression analysis of the vestibular organ of IGF1-/- and IGF1+/+ mice using affymetrix whole transcript arrays

Abstract

Insulin-like growth factor 1(IGF-1) has a central role in mammalian hearing and hearing loss. The auditory and vestibular systems form the inner ear and have a common developmental origin. During chicken early development, IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system. In this study we have compared the whole transcriptome of the vestibular organ from wild type and Igf1-/- null mice at different developmental times. RNA was prepared from E18.5, P15 and P90 vestibular organs of Igf1-/- and Igf1+/+ mice and the transcriptome analyzed in triplicates using Affymetrix® Mouse Gene 1.1 ST Array Plates. These plates are whole-transcript arrays that include probes to measure both messenger (mRNA) and long intergenic noncoding RNA transcripts (lincRNA), with a coverage of over 28 thousand coding transcripts and over seven thousand non-coding transcripts. To describe the number of false positives and quantify uncertainty, the data were analysed and then compared using two different methods VSN-RMA and mmBGX. The morphology of the vestibular organ of both genotypes did not show striking cellular differences. No evident alterations were observed in the vestibular sensory areas of the null mice. Accordingly, these mice did not show a dramatic vestibular phenotype. Finally, functional analysis was carried out on genes that were differentially expressed between genotypes and across time to define new pathways that are involved in the development of the vestibular organ as well as pathways that maybe affected by the lack of IGF-1.