Basement membrane fragility underlies embryonic lethality in fukutin-null mice

Hiroki Kurahashi, Mariko Ikeda, Chikara Meno, Yoshihiro Taniguchi, Satoshi Takeda, Masato Horie, Hiroki Otani, Tatsushi Toda

Research output: Contribution to journalArticle

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Abstract

Fukuyama-type congenital muscular dystrophy (FCMD), associated with brain malformation due to defects in neuronal migration, is caused by mutations in fukutin. Several lines of evidence suggest that the fukutin protein plays a pivotal role in synthesis of O-mannosyl sugar moieties of α-dystroglycan, a cell surface laminin receptor. Here, through targeted disruption of the orthologous mouse fukutin gene, we show that the fukutin protein is essential, as homozygous-null embryos die by E9.5 of gestation. Fukutin-null embryos show phenotypic diversity, features of which include growth retardation, folding of the egg cylinder, leakage of maternal red blood cells into the yolk sac cavity, and an increased number of apoptotic cells in the ectoderm. Loss of immunoreactivity against sugar moieties in α-dystroglycan suggests a reduced laminin-binding capacity. Ultrastructural analysis shows thin and breached basement membranes (BMs). BM fragility may underlie all of these abnormal phenotypes, and maintenance of BM function may require fukutin-mediated glycosylation of α-dystroglycan early in embryonic development.

Original languageEnglish
Pages (from-to)208-217
Number of pages10
JournalNeurobiology of Disease
Volume19
Issue number1-2
DOIs
Publication statusPublished - 01-01-2005

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Dystroglycans
Basement Membrane
Embryonic Structures
Walker-Warburg Syndrome
Laminin Receptors
Yolk Sac
Ectoderm
Cell Surface Receptors
Laminin
Glycosylation
Embryonic Development
Ovum
Proteins
Cell Count
Erythrocytes
Maintenance
Mothers
Phenotype
Pregnancy
Mutation

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this

Kurahashi, Hiroki ; Ikeda, Mariko ; Meno, Chikara ; Taniguchi, Yoshihiro ; Takeda, Satoshi ; Horie, Masato ; Otani, Hiroki ; Toda, Tatsushi. / Basement membrane fragility underlies embryonic lethality in fukutin-null mice. In: Neurobiology of Disease. 2005 ; Vol. 19, No. 1-2. pp. 208-217.
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Basement membrane fragility underlies embryonic lethality in fukutin-null mice. / Kurahashi, Hiroki; Ikeda, Mariko; Meno, Chikara; Taniguchi, Yoshihiro; Takeda, Satoshi; Horie, Masato; Otani, Hiroki; Toda, Tatsushi.

In: Neurobiology of Disease, Vol. 19, No. 1-2, 01.01.2005, p. 208-217.

Research output: Contribution to journalArticle

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