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C-RAF deficiency causes cochlear abnormalities and profound sensorineural deafness in the mice

AuthorsIriarte, Rocío de ; Magariños, Marta ; Rapp, Ulf R.; Varela-Nieto, Isabel
Issue Date2012
CitationIEB (2012)
Abstract[Introduction]: Insulin-like growth factor I (IGF-I) is fundamental for neurogenesis and neuronal differentiation during inner ear development. IGF- I deficiency is associated with deafness in man and mice. IGF-I binds to its high affinity receptor and activates downstream signaling as the RAFMEK-ERK pathway. RAF kinases are essential for cell proliferation, survival and differentiation during development and in the adult tissues homeostasis. RAF proteins have redundant but also specific cellular and tissular functions. In the developing chicken inner ear the activation of C-RAF and B-RAF are critical for otic neurogenesis. [Material and Methods]: To further study the role of RAF kinases in the auditory receptor, we have analysed C-RAF mRNA and protein expression patterns in the mouse inner ear along development. To explore its functional relevance we have preformed ABR to study the auditory phenotype of the C-Raf -/- null mouse. [Results]: Our results show that C-RAF is differentially expressed and that the protein is active and able to phosphorylate downstream substrates. Mutants present an all-frequency profound sensorineural hearing loss with a mean auditory threshold of 90 dB SPL. The study of the general cochlear cytoarchitecture indicates that the main structures and cell types have been formed, although the expression of proteins essential for hearing is altered. Thus the levels of the Kir4.1 potassium channel in the stria vascularis are reduced in the C-Raf-/- null when compared to the wild type littermates. [Conclusions]: In summary, these results show that C-RAF is expressed in the developing cochlea and that its activity is essential for the onset of hearing.
DescriptionTrabajo presentado al 49th Workshop on Inner Ear Biology celebrada en Alemania del 30 de septiembre al 2 de octubre de 2012.
Publisher version (URL)http://www.conventus.de/ieb2012/
Appears in Collections:(IIBM) Comunicaciones congresos
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