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Publication : Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear.

First Author  Mendus D Year  2014
Journal  Eur J Neurosci Volume  39
Issue  8 Pages  1256-67
PubMed ID  24460873 Mgi Jnum  J:227951
Mgi Id  MGI:5704040 Doi  10.1111/ejn.12486
Citation  Mendus D, et al. (2014) Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear. Eur J Neurosci 39(8):1256-67
abstractText  Thrombospondins (TSPs) constitute a family of secreted extracellular matrix proteins that have been shown to be involved in the formation of synapses in the central nervous system. In this study, we show that TSP1 and TSP2 are expressed in the cochlea, and offer the first description of their putative roles in afferent synapse development and function in the inner ear. We examined mice with deletions of TSP1, TSP2 and both (TSP1/TSP2) for inner ear development and function. Immunostaining for synaptic markers indicated a significant decrease in the number of formed afferent synapses in the cochleae of TSP2 and TSP1/TSP2 knockout (KO) mice at postnatal day (P)29. In functional studies, TSP2 and TSP1/TSP2 KO mice showed elevated auditory brainstem response (ABR) thresholds as compared with wild-type littermates, starting at P15, with the most severe phenotype being seen for TSP1/TSP2 KO mice. TSP1/TSP2 KO mice also showed reduced wave I amplitudes of ABRs and vestibular evoked potentials, suggesting synaptic dysfunction in both the auditory and vestibular systems. Whereas ABR thresholds in TSP1 KO mice were relatively unaffected at early ages, TSP1/TSP2 KO mice showed the most severe phenotype among all of the genotypes tested, suggesting functional redundancy between the two genes. On the basis of the above results, we propose that TSPs play an important role in afferent synapse development and function of the inner ear.
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