Increased noise sensitivity and altered inner ear MENA distribution in VASP-/- mice.
Vasodilator-stimulated phosphoprotein (VASP) and mammalian-enabled protein (MENA) share similar cellular localisation and functions (signal transduction pathways, regulation of actin cytoskeleton dynamics). Functional substitution and compensation among Ena/VASP proteins have been proposed as the reason for the absence of major morphological and functional deficits in VASP-/- mice. The aim of this study was to investigate VASP expression in the mouse cochlea, to analyse cochlear function in VASP-/- mice compared with wildtype mice, and to analyse cochlear MENA distribution taking into account that MENA protein might compensate VASP loss in the cochlea of VASP-/- mice. We confirmed specific VASP expression in the pillar cells of the mice organ of Corti as previously reported for rat cochlea. By analysing the hearing function in VASP-/- mice, we found no differences in auditory brainstem responses and distortion product otoacoustic emissions from those of wildtype mice but evidence for an increased noise sensitivity at lower frequencies. When MENA protein levels in cochlea tissue were tested in mutant and wildtype mice by Western blot analysis, no significant differences were found, as was also seen with regard to MENA mRNA levels in laser-microdissected single pillar cells. Most surprisingly, however, MENA protein was absent in pillar cells of VASP-/- mice, whereas it was detected in other cochlear cells. The finding of a cell-specific, and not organ-specific, redundancy of MENA protein expression noted for the first time in VASP-/- mice is proposed as the reason for the observed distinct cochlear phenotype.
Schick
Bernhard
B
Department of Otolaryngology, University Erlangen-Nürnberg, Waldstrasse 1, 91054, Erlangen, Germany. bernhard.schick@hno.imed.uni-erlangen.de
Praetorius
Mark
M
Eigenthaler
Martin
M
Jung
Volker
V
Müller
Marcus
M
Walter
Ulrich
U
Knipper
Marlies
M
D000818:Animals; D001309:Auditory Threshold / Q000502:physiology*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D015870:Gene Expression; D006317:Hearing Loss, Noise-Induced / Q000503:physiopathology; D017403:In Situ Hybridization; D007760:Labyrinth Supporting Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D008840:Microfilament Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098662:Vasodilator-Stimulated Phosphoprotein