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

Isabel Martinez-Garay, Luiz G. Guidi, Zoe G. Holloway, Melissa A. G. Bailey, Daniel Lyngholm, Tomasz Schneider, Timothy Donnison, Simon J. B. Butt, Antonio Velayos-Baeza, Zoltán Molnár, Anthony P. Monaco

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.
LanguageEnglish
Pages1-18
Number of pages18
JournalBrain Structure and Function
DOIs
Publication statusPublished - 10 Aug 2016

Fingerprint

Dyslexia
Knockout Mice
Neurons
Genes
Brain
Sensory Gating
Proteins
Gene Targeting
Neurogenesis
RNA Interference
Embryonic Structures
Anxiety

Keywords

  • kiaa0319
  • dyslexia
  • neuronal migration
  • anatomy
  • cerebral cortex
  • development

Cite this

Martinez-Garay, I., Guidi, L. G., Holloway, Z. G., Bailey, M. A. G., Lyngholm, D., Schneider, T., ... Monaco, A. P. (2016). Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice. Brain Structure and Function , 1-18. https://doi.org/10.1007/s00429-016-1282-1
Martinez-Garay, Isabel ; Guidi, Luiz G. ; Holloway, Zoe G. ; Bailey, Melissa A. G. ; Lyngholm, Daniel ; Schneider, Tomasz ; Donnison, Timothy ; Butt, Simon J. B. ; Velayos-Baeza, Antonio ; Molnár, Zoltán ; Monaco, Anthony P. / Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice. In: Brain Structure and Function . 2016 ; pp. 1-18.
@article{56162956c99646e6b7d9a57641e6064b,
title = "Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice",
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.",
keywords = "kiaa0319, dyslexia, neuronal migration, anatomy, cerebral cortex, development",
author = "Isabel Martinez-Garay and Guidi, {Luiz G.} and Holloway, {Zoe G.} and Bailey, {Melissa A. G.} and Daniel Lyngholm and Tomasz Schneider and Timothy Donnison and Butt, {Simon J. B.} and Antonio Velayos-Baeza and Zolt{\'a}n Moln{\'a}r and Monaco, {Anthony P.}",
year = "2016",
month = "8",
day = "10",
doi = "10.1007/s00429-016-1282-1",
language = "English",
pages = "1--18",
journal = "Brain Structure and Function",
issn = "1863-2653",

}

Martinez-Garay, I, Guidi, LG, Holloway, ZG, Bailey, MAG, Lyngholm, D, Schneider, T, Donnison, T, Butt, SJB, Velayos-Baeza, A, Molnár, Z & Monaco, AP 2016, 'Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice' Brain Structure and Function , pp. 1-18. https://doi.org/10.1007/s00429-016-1282-1

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.; Velayos-Baeza, Antonio; Molnár, Zoltán; Monaco, Anthony P.

In: Brain Structure and Function , 10.08.2016, p. 1-18.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice

AU - Martinez-Garay, Isabel

AU - Guidi, Luiz G.

AU - Holloway, Zoe G.

AU - Bailey, Melissa A. G.

AU - Lyngholm, Daniel

AU - Schneider, Tomasz

AU - Donnison, Timothy

AU - Butt, Simon J. B.

AU - Velayos-Baeza, Antonio

AU - Molnár, Zoltán

AU - Monaco, Anthony P.

PY - 2016/8/10

Y1 - 2016/8/10

N2 - 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.

AB - 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.

KW - kiaa0319

KW - dyslexia

KW - neuronal migration

KW - anatomy

KW - cerebral cortex

KW - development

U2 - 10.1007/s00429-016-1282-1

DO - 10.1007/s00429-016-1282-1

M3 - Article

SP - 1

EP - 18

JO - Brain Structure and Function

T2 - Brain Structure and Function

JF - Brain Structure and Function

SN - 1863-2653

ER -