Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish

Abstract

Hearing loss is one of the most prevalent human birth defects. Genetic factors contribute to the pathogenesis of deafness. It is estimated that one-third of deafness genes have already been identified. The current work is an attempt to find novel genes relevant to hearing loss using guilt-by-profiling and guilt-by-association bioinformatics analyses of approximately 80 known non-syndromic hereditary hearing loss (NSHL) genes. Among the 300 newly identified candidate deafness genes, slc26a2 were selected for functional studies in zebrafish. The slc26a2 gene was knocked down using an antisense morpholino (MO), and significant defects were observed in otolith patterns, semicircular canal morphology, and lateral neuromast distributions in morphants. Loss-of-function defects are caused primarily by apoptosis, and morphants are insensitive to sound stimulation and imbalanced swimming behaviours. Morphant defects were found to be partially rescued by co-injection of human SLC26A2 mRNA. All the results suggest that bioinformatics is capable of predicting new deafness genes and this showed slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment.

Interactions of Environmental Chemicals and Natural Products With ABC and SLC Transporters in the Digestive System of Aquatic Organisms

“…In fish, SLCs play an important role in organismal development and transport of endogenous compounds to allow for proper development of swim bladders ( Kim et al, 2020 ), inner ears ( Liu et al, 2015 ), kidneys ( Schoels et al, 2021 ), and normal development of embryos ( Takesono et al, 2012 ). In addition, SLCs play a crucial role in intestinal absorption and transport of amino acids and other physiological compounds, including thyroid hormones ( Arjona et al, 2011 ; Muzzio et al, 2014 ), iron ( Cooper et al, 2007 ), zinc ( Yan et al, 2012 ; Jiang et al, 2014 ), coenzyme-A ( Kim et al, 2020 ), and amino acids and peptides ( Romano et al, 2006 , 2014 ; Verri et al, 2010 , 2017 ; Margheritis et al, 2013 ; Rimoldi et al, 2015 ; Song et al, 2017 ; To et al, 2019 ; Vacca et al, 2019 ).…”

The Roles of Solute Carriers in Auditory Function

“…In addition to the two members, SLC26A4 and SLC26A5, discussed above, another gene, SLC26A2, encoding for a sulfate/ chloride transporter, may be associated with hearing loss. In zebrafish, the slc26a2 gene was proven to be critical for otic development and hair cell survival, and loss of function of slc26a2 led to defective auditory organ development and impaired hearing (Liu et al, 2015).…”

Chondrodysplasias With Multiple Dislocations Caused by Defects in Glycosaminoglycan Synthesis

“…Moreover, growth plate cartilage showed reduced toluidine blue staining, chondrocytes of irregular size, and delayed secondary ossification center formation (Forlino et al, 2005 ). Slc26a2 morphant zebrafish exhibited, on the other hand, an abnormal otic development (Liu et al, 2015 ).…”