title: Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development.
abstract: Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal-recessive disorders in Japan, is characterized by congenital muscular dystrophy associated with brain malformation due to a defect during neuronal migration. Through positional cloning, we previously identified the gene for FCMD, which encodes the fukutin protein. Here we report that chimeric mice generated using embryonic stem cells targeted for both fukutin alleles develop severe muscular dystrophy, with the selective deficiency of alpha-dystroglycan and its laminin-binding activity. In addition, these mice showed laminar disorganization of the cortical structures in the brain with impaired laminin assembly, focal interhemispheric fusion, and hippocampal and cerebellar dysgenesis. Further, chimeric mice showed anomaly of the lens, loss of laminar structure in the retina, and retinal detachment. These results indicate that fukutin is necessary for the maintenance of muscle integrity, cortical histiogenesis, and normal ocular development and suggest the functional linkage between fukutin and alpha-dystroglycan.
authors.affiliation: Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.forename: Mari
authors.initials: M
authors.lastname: Kondo
authors.forename: Junko
authors.initials: J
authors.lastname: Sasaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kano
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Misaki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fukui
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Masaji
authors.initials: M
authors.lastname: Tachikawa
authors.forename: Michihiro
authors.initials: M
authors.lastname: Imamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Teruo
authors.initials: T
authors.lastname: Shimizu
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Murakami
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Sunada
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujikado
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Matsumura
authors.forename: Toshio
authors.initials: T
authors.lastname: Terashima
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
mesh_terms: D000818:Animals; D001519:Behavior; D001921:Brain / Q000254:growth & development* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D004596:Electroretinography; D005123:Eye / Q000254:growth & development*; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology; D009799:Ocular Physiological Phenomena; D010641:Phenotype; D011506:Proteins / Q000502:physiology*; D014166:Transferases
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D007797:Laminin; D008562:Membrane Glycoproteins; D011506:Proteins; D049030:Dystroglycans; C491879:Fcmd protein, mouse; D014166:Transferases