PRG4 (proteoglycan 4) has been identified as megakaryocyte stimulating fact
or and articular superficial zone protein. PRG4 has characteristic motifs i
ncluding somatomedin B and hemopexin domains, a chondroitin sulfate-attachm
ent site and mucin-like repeats. During a screen of genes implicated in ect
opic ossification, we found a novel mouse gene highly homologous to human a
nd bovine PRG4 genes. Here, we report isolation, characterization and mappi
ng of the gene, Prg4 together with characterization of its human orthologue
. Prg4 cDNA was 3,320 bp long, encoding a 1,054 amino-acid protein. Human a
nd mouse PRG4 genes each consisting of 12 exons spanned 18 and 16 kb, respe
ctively. Characteristic motifs were conserved across species; however, the
mucin-like repeat regions were highly diverse in length between species wit
h a tendency that larger animals had longer repeats. Expression of human an
d mouse PRG4 genes was similar and found not only in cartilage, but also in
liver, heart, lung, and bone. Expression of the mouse gene increased with
progression of ectopic ossification. Multiple tissue-specific splicing vari
ants lacking some of the motifs were found in both human and mouse. Althoug
h a specific role in the articular joint has previously been reported, the
presence of multi-functional motifs as well as unique expression and altern
ative splicing patterns suggest that PRG4 functions in several distinctive
biological process including regulation of ossification. Copyright (C) 2000
S. Karger AG, Basel.