Mouse lipocortin I gene structure and chromosomal assignment: gene duplication and the origins of a gene family.

Using cDNA probes obtained from library screening and anchored polymerase chain reaction, we have isolated and characterized three overlapping mouse genomic clones that contain the mouse lipocortin I (Lipo I) structural gene. Restriction enzyme mapping, Southern blotting, and DNA sequencing were carried out on the cloned genomic DNA. Lipo I spans about 17 kb and is divided into 13 exons encoding a protein of 346 amino acid residues. The promoter region of the gene has a TATA box and a CCAAT box located upstream of the transcription initiation site at -31 and -76 bp, respectively. Analysis of the strain distribution pattern of Lipo 1 in BXD and AKXD collections of recombinant inbred strains establishes that Lipo I is located on chromosome 19 in close proximity to Ea-4. While no striking relationship exists between the exon/intron structure of the gene and the four repeated 70-amino-acid domains of the protein, three of the four 17-amino-acid repeats believed to be responsible for Ca2+/phospholipid binding are encoded by the last codon of one exon and the first 16 codons of the following exon. This pattern supports the gene duplication theory, and the similarity in gene structure between mouse Lipo I and Lipo II suggests they have a recent evolutionary ancestor.