Atp6v1b2Plays Important Roles in the Early Development of Hearing, the Pectoral Fin, the Cardiovascular System, and the Swim Bladder of the Zebrafish, Supporting a Role for the Gene in Syndromic Hearing Loss

Abstract

Background:The ATP6V1B2 gene plays a critical role in the auditory system, and a mutation in this gene is one genetic cause of DDOD syndrome (Dominant deafness-onychodystrophy syndrome, MIM 124480) and ZLS (Zimmermann-Laband syndrome, MIM 135500). However, whether and how ATP6V1B2 is involved in the development of other organs remains unknown. In the present study, we explored the effect of atp6v1b2 knockdown on early zebrafish development and verified that this gene plays a role in syndromic hearing loss.Methods: Three morpholinos (two splice-blocking, one translation-blocking) and the atp6v1b2 c.1516 C>T plasmid were used to knockdown or overexpress atp6v1b2 in zebrafish after microinjection of fertilised embryos. Control and atp6v1b2 embryo morphants were evaluated 6 days post-fertilisation in terms of motility, apoptosis, pectoral fin development, and hair cell number.Results: Atp6v1b2-knockdown zebrafish exhibited decreased body length, pericardial oedema, hair cell loss, a non-inflated swim bladder, and shorter pectoral fins; the first three phenotypes were also evident in fish overexpressing the gene. Conclusions:Atp6v1b2 plays important roles in the development of hearing, the pectoral fin, the cardiovascular system, and the swim bladder, thereby supporting a role for this gene in syndromic hearing loss.

Zika Infection Disrupts Proteins Involved in the Neurosensory System

“…Several of these proteins play key roles in neurosensory development. COMT (Catechol O-methyltransferase), a kinase reduced more than 1.5-fold at 24 hpi, is involved in neurosensory responses like nociception, balance, hearing, and catecholamine metabolism (Fernandez-Garcia et al, 2016;Yuan et al, 2015). Du and co-workers documented several severe malformations in a COMT missense murine model, including abnormal auditory startle response, impaired movement behavior, and loss of inner and outer hair cells with degeneration of cochlear neurons and vestibular defects, collectively causing deafness and degeneration of the vestibular sensory/balancing system in mice by 8 weeks of age (Menendez et al, 2017).…”