Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice

Martinez Garay, Isabel, Guidi, Luiz G., Holloway, Zoe G., Bailey, Melissa A. G., Lyngholm, Daniel, Schneider, Tomasz, Donnison, Timothy, Butt, Simon J. B., Monaco, Anthony P., Molnár, Zoltán and Velayos-Baeza, Antonio 2017. Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice. Brain Structure and Function 222 (3) , pp. 1367-1384. 10.1007/s00429-016-1282-1

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (16MB) | Preview

Abstract

Developmental dyslexia is a common disorder with a strong genetic component, but the underlying molecular mechanisms are still unknown. Several candidate dyslexia-susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified in humans. RNA interference experiments targeting these genes in rat embryos have shown impairments in neuronal migration, suggesting that defects in radial cortical migration could be involved in the disease mechanism of dyslexia. Here we present the first characterisation of a Kiaa0319 knockout mouse line. Animals lacking KIAA0319 protein do not show anatomical abnormalities in any of the layered structures of the brain. Neurogenesis and radial migration of cortical projection neurons are not altered, and the intrinsic electrophysiological properties of Kiaa0319-deficient neurons do not differ from those of wild-type neurons. Kiaa0319 overexpression in cortex delays radial migration, but does not affect final neuronal position. However, knockout animals show subtle differences suggesting possible alterations in anxiety-related behaviour and in sensorimotor gating. Our results do not reveal a migration disorder in the mouse model, adding to the body of evidence available for Dcdc2 and Dyx1c1 that, unlike in the rat in utero knockdown models, the dyslexia-susceptibility candidate mouse homolog genes do not play an evident role in neuronal migration. However, KIAA0319 protein expression seems to be restricted to the brain, not only in early developmental stages but also in adult mice, indicative of a role of this protein in brain function. The constitutive and conditional knockout lines reported here will be useful tools for further functional analyses of Kiaa0319.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: Kiaa0319 Dyslexia Neuronal migration Anatomy Cerebral cortex Development
Publisher: Springer
ISSN: 1863-2653
Date of First Compliant Deposit: 4 November 2016
Date of Acceptance: 26 July 2016
Last Modified: 04 Jun 2017 15:03
URI: http://orca.cf.ac.uk/id/eprint/95760

Citation Data

Cited 6 times in Google Scholar. View in Google Scholar

Cited 5 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics