Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L Have Unaffected Neuronal Migration but Display Abnormal Auditory Processing

Overview

Journal Cereb Cortex

Publisher Oxford University Press

Specialty Neurology

Date 2017 Oct 19

PMID 29045729

Citations 10

Authors

Luiz G Guidi

Jane Mattley

Isabel Martinez-Garay

Anthony P Monaco

Jennifer F Linden

Antonio Velayos-Baeza

Zoltan Molnar

Affiliations

Soon will be listed here.

Abstract

Developmental dyslexia is a neurodevelopmental disorder that affects reading ability caused by genetic and non-genetic factors. Amongst the susceptibility genes identified to date, KIAA0319 is a prime candidate. RNA-interference experiments in rats suggested its involvement in cortical migration but we could not confirm these findings in Kiaa0319-mutant mice. Given its homologous gene Kiaa0319L (AU040320) has also been proposed to play a role in neuronal migration, we interrogated whether absence of AU040320 alone or together with KIAA0319 affects migration in the developing brain. Analyses of AU040320 and double Kiaa0319;AU040320 knockouts (dKO) revealed no evidence for impaired cortical lamination, neuronal migration, neurogenesis or other anatomical abnormalities. However, dKO mice displayed an auditory deficit in a behavioral gap-in-noise detection task. In addition, recordings of click-evoked auditory brainstem responses revealed suprathreshold deficits in wave III amplitude in AU040320-KO mice, and more general deficits in dKOs. These findings suggest that absence of AU040320 disrupts firing and/or synchrony of activity in the auditory brainstem, while loss of both proteins might affect both peripheral and central auditory function. Overall, these results stand against the proposed role of KIAA0319 and AU040320 in neuronal migration and outline their relationship with deficits in the auditory system.

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