Cloning, characterization, and chromosomal assignment of the human ortholog of murine Zfp-37, a candidate gene for Nager syndrome

Abstract.

In an effort to identify putative transcription factors involved in chondrocyte differentiation during human endochondral bone formation, a human fetal cartilage-specific cDNA library was screened with a degenerate oligonucleotide probe corresponding to a conserved stretch of eight amino acids from the zinc finger region of the Drosophila Krüppel gene family of DNA-binding proteins. Using this strategy, we have identified a novel zinc finger gene ZFP-37. ZFP-37 corresponds to a putative transcription factor containing 12 tandemly repeated zinc finger motifs and a Krüppel-associated box (KRAB) domain. The KRAB domain has been reported to function as a transcriptional repressor and is located in the amino terminus, while the zinc finger repeats are positioned at the carboxy-terminal end of ZFP-37. Gene mapping with a somatic cell hybrid panel and fluorescence in situ hybridization (FISH) localized ZFP-37 to human Chr 9q32. The gene is expressed at low level as a 3.2-kb mRNA in several tissues including fetal human cartilage. Sequence comparison revealed that ZFP-37 may represent the human homolog of the mouse gene Zfp-37. The map location and expression pattern suggest ZFP-37 as a candidate gene for a craniofacial-limb malformation, Nager syndrome (acrofacial dysostosis).