Linked Life Data

9739041

Source:http://linkedlifedata.com/resource/pubmed/id/9739041

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pubmed-article:9739041pubmed:abstractTextWinged helix transcription factors play important roles in cellular differentiation and cell-specific gene expression. To define the role of the winged helix factor hepatocyte nuclear factor/forkhead homologue (HFH)-4, a targeted mutation was created in the mouse hfh-4 gene. No expression of HFH-4 was detected in hfh-4(-)/- mice by RNA blot analysis, in situ hybridization, or RT-PCR. hfh-4(-)/- mice were noted to have abnormalities of organ situs consistent with random determination of left-right asymmetry. In addition, a complete absence of cilia was noted in hfh-4(-)/- mice. The hfh-4 gene is thus essential for nonrandom determination of left-right asymmetry and development of ciliated cells. Homozygous mutant mice also exhibited prenatal and postnatal growth failure, perinatal lethality and, in some cases, hydrocephalus. RT-PCR revealed an absence of left-right dynein (lrd) expression in the embryonic lungs of hfh-4(-)/- mice, suggesting that HFH-4 may act by regulating expression of members of the dynein family of genes. The abnormalities in ciliary development and organ situs in hfh-4(-)/- mice are similar to those observed in human congenital syndromes such as Kartagener syndrome. Targeted mutation of hfh-4 thus provides a model for elucidating the mechanisms regulating ciliary development and determination of left-right asymmetry.lld:pubmed
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pubmed-article:9739041pubmed:authorpubmed-author:ChenJJlld:pubmed
pubmed-article:9739041pubmed:authorpubmed-author:HebertJ LJLlld:pubmed
pubmed-article:9739041pubmed:authorpubmed-author:HackettB PBPlld:pubmed
pubmed-article:9739041pubmed:authorpubmed-author:KnowlesH JHJlld:pubmed
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pubmed-article:9739041pubmed:dateRevised2009-11-19lld:pubmed
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