| Autor: |
Martinez-Garay I; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK.; Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff, UK., Guidi LG; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK.; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK., Holloway ZG; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK., Bailey MA; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK., Lyngholm D; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK.; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK., Schneider T; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK., Donnison T; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK., Butt SJ; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK., Monaco AP; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. anthony.monaco@tufts.edu.; Office of the President, Ballou Hall, Tufts University, Medford, MA, 02155, USA. anthony.monaco@tufts.edu., Molnár Z; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, OX1 3QX, UK. Zoltan.Molnar@dpag.ox.ac.uk., Velayos-Baeza A; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. avelayos@well.ox.ac.uk. |
| Abstrakt: |
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. |
Full text from SpringerLink