The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus

Tsutomu Kume, Ke Yu Deng, Virginia Winfrey, Douglas B. Gould, Michael A. Walter, Brigid L M Hogan

Research output: Contribution to journalArticlepeer-review

293 Scopus citations

Abstract

Mf1 encodes a forkhead/winged helix transcription factor expressed in many embryonic tissues, including prechondrogenic mesenchyme, periocular mesenchyme, meninges, endothelial cells, and kidney. Homozygous null Mf1(lacZ) mice die at birth with hydrocephalus, eye defects, and multiple skeletal abnormalities identical to those of the classical mutant, congenital hydrocephalus. We show that congenital hydrocephalus involves a point mutation in Mf1, generating a truncated protein lacking the DNA-binding domain. Mesenchyme cells from Mf1(lacZ) embryos differentiate poorly into cartilage in micromass culture and do not respond to added BMP2 and TGFβ1. The differentiation of arachnoid cells in the mutant meninges is also abnormal. The human Mf1 homolog FREAC3 is a candidate gene for ocular dysgenesis and glaucoma mapping to chromosome 6p25-pter, and deletions of this region are associated with multiple developmental disorders, including hydrocephaly and eye defects.

Original languageEnglish (US)
Pages (from-to)985-996
Number of pages12
JournalCell
Volume93
Issue number6
DOIs
StatePublished - Jun 12 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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