| First Author | Chen J | Year | 1998 |
| Journal | J Clin Invest | Volume | 102 |
| Issue | 6 | Pages | 1077-82 |
| PubMed ID | 9739041 | Mgi Jnum | J:50025 |
| Mgi Id | MGI:1289759 | Doi | 10.1172/JCI4786 |
| Citation | Chen J, et al. (1998) Mutation of the mouse hepatocyte nuclear factor/forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry. J Clin Invest 102(6):1077-82 |
| abstractText | Winged 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 hflt-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. |
