Basement membrane fragility underlies embryonic lethality in fukutin-null mice

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

研究成果: Article査読

59 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)208-217
ページ数10
ジャーナルNeurobiology of Disease
19
1-2
DOI
出版ステータスPublished - 2005

All Science Journal Classification (ASJC) codes

  • 神経学

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