Epiprofin, a Kruppel-like factor, is essential for hair, tooth, and limb development

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We identified a cDNA clone for a nuclear factor that we named epiprofin by differential hybridization using DNA microarrays from an embryonic day 1 9.5 mouse molar cDNA library. Full-length cloning and sequencing revealed that epiprofin encodes a member of the Kruppel-Like Factor (KLF) family containing three characteristic C2H2-type zinc-finger motifs. Except for its 5' terminal sequence, the epiprofin mRNA sequence is almost identical to the predicted sequence of KLF14/SP6, which was previously identified in EST databases and GenBank through a sequence homology search for an Sp1 zinc-finger DNA binding domain. In situ hybridization revealed that epiprofin mRNA is expressed by proliferating hair follicle matrix epithelium and also dental epithelium. In addition, whole-mount in situ hybridization showed transient expression of epiprofin mRNA in cells of the apical ectodermal ridge (AER) in developing limb and the posterior neuropore. Transfection of an epiprofin expression vector showed that epiprofin is localized in the nucleus and promotes cell proliferation, suggesting that epiprofin is a highly cell- and tissue-specific nuclear protein expressed primarily by proliferating epithelial cells of hair follicle, tooth, and limb. Homozygous epiprofin knockout mice survive but are hairless, toothless, and have fusion and/or missing digits, indicating the essential role of epiprofin in the development of these tissues.
2004-06-03