Comparative gene expression study of the vestibular organ of the Igf1 deficient mouse using whole-transcript arrays.
The auditory and vestibular organs form the inner ear and have a common developmental origin. Insulin like growth factor 1 (IGF-1) has a central role in the development of the cochlea and maintenance of hearing. Its deficiency causes sensorineural hearing loss in man and mice. 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(-/-) mice at different developmental and postnatal times. RNA was prepared from E18.5, P15 and P90 vestibular organs of Igf1(-/-) and Igf1(+/+) mice and the transcriptome analysed 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 non-coding RNA transcripts (lincRNA), with a coverage of over 28 thousand coding transcripts and over 7 thousands non-coding transcripts. Given the complexity of the data we used two different methods VSN-RMA and mmBGX to analyse and compare the data. This is to better evaluate the number of false positives and to quantify uncertainty of low signals. We identified a number of differentially expressed genes that we described using functional analysis and validated using RT-qPCR. The morphology of the vestibular organ did not show differences between genotypes and no evident alterations were observed in the vestibular sensory areas of the null mice. However, well-defined cellular alterations were found in the vestibular neurons with respect their number and size. Although these mice did not show a dramatic vestibular phenotype, we conducted a functional analysis on differentially expressed genes between genotypes and across time. This was with the aim to identify 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 and be associated to the morphological changes of the vestibular neurons that we observed in the Igf1(-/-) mice.
Neurobiology of Hearing, Department of Endocrine and Nervous System Pathophysiology, Alberto Sols Biomedical Research Institute (IIBM), CSIC-UAM, Madrid, Spain; Biomedical Research Networking Center on Rare Diseases (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain; IdiPAZ Institute for Health Research, Madrid, Spain.
Lourdes
L
Rodríguez-de la Rosa
Neurobiology of Hearing, Department of Endocrine and Nervous System Pathophysiology, Alberto Sols Biomedical Research Institute (IIBM), CSIC-UAM, Madrid, Spain.
Hortensia
H
Sánchez-Calderón
Neurobiology of Hearing, Department of Endocrine and Nervous System Pathophysiology, Alberto Sols Biomedical Research Institute (IIBM), CSIC-UAM, Madrid, Spain; Biomedical Research Networking Center on Rare Diseases (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain; Department of Anatomy, Faculty of Veterinary, Complutense University, Madrid, Spain.
Julio
J
Contreras
Neurobiology of Hearing, Department of Endocrine and Nervous System Pathophysiology, Alberto Sols Biomedical Research Institute (IIBM), CSIC-UAM, Madrid, Spain; Biomedical Research Networking Center on Rare Diseases (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain; IdiPAZ Institute for Health Research, Madrid, Spain.
Silvia
S
Murillo-Cuesta
Department of Anatomy, Faculty of Medicine, Autonomous University, Madrid, Spain.
Sandra
S
Falagan
IdiPAZ Institute for Health Research, Madrid, Spain; Department of Anatomy, Faculty of Medicine, Autonomous University, Madrid, Spain.
Carlos
C
Avendaño
Biomedical Research Networking Center on Rare Diseases (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain; Department of Computational Genomics, Centro de Investigación Príncipe Felipe, Valencia, Spain.
Joaquín
J
Dopazo
Neurobiology of Hearing, Department of Endocrine and Nervous System Pathophysiology, Alberto Sols Biomedical Research Institute (IIBM), CSIC-UAM, Madrid, Spain; Biomedical Research Networking Center on Rare Diseases (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain; IdiPAZ Institute for Health Research, Madrid, Spain.
Isabel
I
Varela-Nieto
Department of Biomedical Science, University of Sheffield, Sheffield, UK. Electronic address: m.milo@sheffield.ac.uk.
Marta
M
Milo
D000818:Animals; D016000:Cluster Analysis; D005189:False Positive Reactions; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D006579:Heterozygote; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D059467:Transcriptome; D014725:Vestibular Nerve / Q000378:metabolism*; D014722:Vestibule, Labyrinth / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D048051:p38 Mitogen-Activated Protein Kinases
Affymetrix mouse gene 1.1. ST arrays; Insulin like growth factor 1; Transcriptomics; mRNAs