Molecular cloning and genomic structure of human Frizzled-3 at chromosome 8p21

WNT receptors encoded by the Frizzled genes are implicated in carcinogenesi s as well as in embryonic development. Human Frizzled-3 (FZD3) gene, encodi ng seven-transmembrane receptor with the N-terminal cysteine-rich domain, h as been cloned and characterized. Expression of the FZD3 mRNAs was investig ated by using three FZD3 specific probes: HF3S1, corresponding 60 the 5'-UT R and a part of the coding region; HF3S2, corresponding to a part of the co ding region; HF3S3, corresponding to the 3'-UTR. HF3S1 and HF3S2 hybridized to the 14.0-, 9.0-, 4.0- and 1.8-kb FZD3 mRNA, while HF3S3 hybridized to t he 14.0-, 9.0-, and 4.0-kb FZD3 mRNA. The 14.0-kb FZD3 mRNA was the major t ranscript in fetal brain and adult cerebellum, while the 1.8-kb FZD3 mRNA w as the major transcript in adult pancreas, and many cancer cell lines exami ned. The 1.8-kb FZD3 mRNA, alternatively polyadenylated by the internal AAT AAA signal in the coding region, is predicted to encode the truncated FZD3 protein lacking the region through the second extracellular loop to the C-t erminal tail, and might function as the transmembrane-type antagonist for W NTs. The FZD3 gene consists of 8 exons, and has been mapped to human chromo some 8p21. (C) 2000 Academic Press.