Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development

Satoshi Takeda, Mari Kondo, Junko Sasaki, Hiroki Kurahashi, Hiroki Kano, Ken Arai, Kazuyo Misaki, Takehiko Fukui, Kazuhiro Kobayashi, Masaji Tachikawa, Michihiro Imamura, Yusuke Nakamura, Teruo Shimizu, Tatsufumi Murakami, Yoshihide Sunada, Takashi Fujikado, Kiichiro Matsumura, Toshio Terashima, Tatsushi Toda

Research output: Contribution to journalArticle

99 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1449-1459
Number of pages11
JournalHuman molecular genetics
Volume12
Issue number12
Publication statusPublished - 15-06-2003
Externally publishedYes

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Walker-Warburg Syndrome
Dystroglycans
Muscular Dystrophies
Maintenance
Laminin
Muscles
Brain
Retinal Detachment
Embryonic Stem Cells
Lenses
Retina
Organism Cloning
Japan
Alleles
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Takeda, S., Kondo, M., Sasaki, J., Kurahashi, H., Kano, H., Arai, K., ... Toda, T. (2003). Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development. Human molecular genetics, 12(12), 1449-1459.
Takeda, Satoshi ; Kondo, Mari ; Sasaki, Junko ; Kurahashi, Hiroki ; Kano, Hiroki ; Arai, Ken ; Misaki, Kazuyo ; Fukui, Takehiko ; Kobayashi, Kazuhiro ; Tachikawa, Masaji ; Imamura, Michihiro ; Nakamura, Yusuke ; Shimizu, Teruo ; Murakami, Tatsufumi ; Sunada, Yoshihide ; Fujikado, Takashi ; Matsumura, Kiichiro ; Terashima, Toshio ; Toda, Tatsushi. / Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development. In: Human molecular genetics. 2003 ; Vol. 12, No. 12. pp. 1449-1459.
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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 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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Takeda, S, Kondo, M, Sasaki, J, Kurahashi, H, Kano, H, Arai, K, Misaki, K, Fukui, T, Kobayashi, K, Tachikawa, M, Imamura, M, Nakamura, Y, Shimizu, T, Murakami, T, Sunada, Y, Fujikado, T, Matsumura, K, Terashima, T & Toda, T 2003, 'Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development', Human molecular genetics, vol. 12, no. 12, pp. 1449-1459.

Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development. / Takeda, Satoshi; Kondo, Mari; Sasaki, Junko; Kurahashi, Hiroki; Kano, Hiroki; Arai, Ken; Misaki, Kazuyo; Fukui, Takehiko; Kobayashi, Kazuhiro; Tachikawa, Masaji; Imamura, Michihiro; Nakamura, Yusuke; Shimizu, Teruo; Murakami, Tatsufumi; Sunada, Yoshihide; Fujikado, Takashi; Matsumura, Kiichiro; Terashima, Toshio; Toda, Tatsushi.

In: Human molecular genetics, Vol. 12, No. 12, 15.06.2003, p. 1449-1459.

Research output: Contribution to journalArticle

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

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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