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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-28
pubmed:abstractText
Histone methylation is the important transcription regulatory system that affects mammalian development and cell differentiation. Alterations in epigenetic gene regulation are associated with disease. Fbxl10 (F-box and leucine-rich repeat protein 10) is a JmjC domain-containing histone demethylase. Although Fbxl10 has been implicated in cell cycle regulation, cell death, senescence, and tumorigenesis, these functions are controversial and its physiological function is unclear. To determine the in vivo function of Fbxl10, in this study, we generated a homozygous mutation in the mouse Fbxl10 gene. About half of Fbxl10-deficient mice exhibit failure of neural tube closure, resulting in exencephaly and die shortly after birth. Fbxl10 deficiency also causes retinal coloboma and a curled tail with low penetrances. Fbxl10 mRNA is specifically expressed in the cranial neural folds at E8.5 embryos, and apoptosis increased in the neuroepithelium and mesenchyme of Fbxl10-deficient E9.5 embryos, consistent with neural tube defects found in Fbxl10-deficient mice. Depletion of Fbxl10 induced the increased expression of p19ARF, an inducer of apoptosis, in E8.5 embryos and mouse embryonic fibroblast cells. In addition, the number of mitotic neural progenitor cells is significantly increased in the mutant E14.5 brain. Our findings suggest that the Fbxl10 gene makes important contributions to embryonic neural development by regulating cell proliferation and cell death in mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1095-9327
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
614-24
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly.
pubmed:affiliation
Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't