The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear devel-opment. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

Inner ear and muscle developmental defects in Smpx-deficient zebrafish embryos / A. Ghilardi, A. Diana, R. Bacchetta, N. Santo, M. Ascagni, L. Prosperi, L. Del Giacco. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:12(2021 Jun 17), pp. 6497.1-6497.12. [10.3390/ijms22126497]

Inner ear and muscle developmental defects in Smpx-deficient zebrafish embryos

A. Ghilardi
Investigation
;
A. Diana
Investigation
;
R. Bacchetta;N. Santo;M. Ascagni;L. Del Giacco
Writing – Original Draft Preparation
2021

Abstract

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear devel-opment. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.
hearing loss; myopathy; SMPX; X-chromosome; zebrafish; animals; ear, inner; embryonic development; fluorescent antibody technique; gene expression regulation, developmental; gene knockdown techniques; hair cells, auditory; mechanotransduction, cellular; muscle development; muscle proteins; muscles; organogenesis; phenotype; protein transport; zebrafish
Settore BIO/06 - Anatomia Comparata e Citologia
   Next generation sequencing (NGS) approaches for the identification of novel inherited non-syndromic sensorineural hearing loss (NSHL) related genes
   FONDAZIONE CARIPLO
   2013-0825
17-giu-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/859354
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