TY - JOUR
T1 - Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development
AU - Takeda, Satoshi
AU - Kondo, Mari
AU - Sasaki, Junko
AU - Kurahashi, Hiroki
AU - Kano, Hiroki
AU - Arai, Ken
AU - Misaki, Kazuyo
AU - Fukui, Takehiko
AU - Kobayashi, Kazuhiro
AU - Tachikawa, Masaji
AU - Imamura, Michihiro
AU - Nakamura, Yusuke
AU - Shimizu, Teruo
AU - Murakami, Tatsufumi
AU - Sunada, Yoshihide
AU - Fujikado, Takashi
AU - Matsumura, Kiichiro
AU - Terashima, Toshio
AU - Toda, Tatsushi
N1 - Funding Information:
We thank Drs Masato Horie, Ei-ichi Takahashi, Kenji Araishi, Yukiko K. Hayashi and Eva Engvall for discussion and antibodies; Sawako Muroi, Takashi Wadatsu, Noritaka Koseki, Norihiro Miyazawa, Yuji Fujimori, Tomoyuki Iwanaga, Mai Okano and Kuniko Ohmori for assistance; and Dr Jennifer Logan for editing the manuscript. This study was supported by a Health Science Research Grant, ‘Research on Brain Science’ (H12-Brain-017) and by a Research Grants for Nervous and Mental Disorders (14B-4), both from the Ministry of Health, Labor and Welfare of Japan.
PY - 2003/6/15
Y1 - 2003/6/15
N2 - 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 α-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 α-dystroglycan.
AB - 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 α-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 α-dystroglycan.
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M3 - Article
C2 - 12783852
AN - SCOPUS:10744230411
SN - 0964-6906
VL - 12
SP - 1449
EP - 1459
JO - Human molecular genetics
JF - Human molecular genetics
IS - 12
ER -