The mouse hepatocyte growth factor-encoding gene: structural organization and evolutionary conservation.

A mouse genomic phage library was screened by using a cDNA probe coding for mouse hepatocyte growth factor (HGF). Five overlapping genomic clones which contained the entire mouse HGF gene were isolated and characterized by restriction mapping, Southern hybridization and DNA sequencing. HGF spans about 65 kb and consists of 18 exons separated by 17 introns, similar to its human counterpart. The nucleotide (nt) sequences of the introns at the exon-intron junctions are GT-AG, analogous to those found in other eukaryotic genes. The exon-intron gene organization of HGF is highly homologous to that of several other genes encoding kringle-containing proteins, especially HGF-like protein and plasminogen. This result suggests that HGF probably evolved through gene duplication and/or exon shuffling events from an ancestral gene. Southern hybridization of genomic DNA from different species revealed that a high degree of homology exists among a variety of vertebrates, including chicken, when a mouse HGF cDNA was used as a probe. This evolutionary conservation of HGF strongly suggests that the protein may play an important role in normal cell physiology. Our current results on mouse HGF structure provide basic and detailed information to carry out further manipulation, such as gene targeting.