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

Ghilardi A.;Diana A.;Bacchetta R.;Santo N.;Ascagni M.;Del Giacco L.
2021-06-17

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
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Article (author)
File in questo prodotto:
File Dimensione Formato  
ijms-22-06497.pdf

accesso aperto

2.19 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/859354
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
social impact