title: Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry.
abstract: Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors.
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hiraoka
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sumiyoshi
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Hiroi
authors.initials: H
authors.lastname: Nonaka
authors.affiliation: Department of Developmental Neuroscience, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Kikkawa
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kawashima
authors.affiliation: Department of Developmental Neuroscience, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000196:embryology* / Q000254:growth & development*; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000473:pathology; D006579:Heterozygote; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D000071841:PAX6 Transcription Factor / Q000235:genetics* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D012984:Software; D066127:White Matter / Q000473:pathology
chemical_list: D000071841:PAX6 Transcription Factor; C000605733:Pax6 protein, rat