Sulfation of proteoglycans is a very important posttranslational modification in chondrocyte growth and development. The enzyme 3'-phosphoadenosine 5'-phosphosulfate synthase (PAPSS) catalyzes the biosynthesis of PAPS (3'-phosphoadenosine 5'-phosphosulfate), which serves as the universal sulfate donor compound for all sulfotransferase reactions (Schwartz and Domowicz [2002] Glycobiology 109:143-151). Two major isoenzymes, PAPS synthase 1 (PAPSS1) and PAPS synthase 2 (PAPSS2) were identified in higher organisms for the synthesis of PAPS. PAPSS1 is the more prominent isoform and is ubiquitously expressed in human adult tissues, including cartilage, while PAPSS2 shows a more restricted expression pattern and appears to be the major variant in growth plate cartilage (Fuda et al. [2002] Biochem J 365(Pt 2):497-504). Mutations within the murine and the human PAPSS2 genes are responsible for diseases affecting the skeletal system (Kurima et al. [1998] Proc Natl Acad Sci USA 95:8681-8685; ul Haque et al. [1998] Nat Genet 20:157-162), like the spondyloepimetaphyseal dysplasia (SEMD) Pakistani type. To further elucidate the function of Papss2 within the developing skeleton, we investigated the expression pattern of the murine gene at different developmental stages. We detected Papss2 mRNA starting from 11.5 days post coitum (dpc) at the sites of first chondrogenic condensations and the expression continued in all cartilaginous elements tested of 12.5 dpc, 13.5 dpc, 16.5 dpc embryos, and newborn mice. Papss2 transcripts were also observed in other tissues such as heart, tongue, kidney, and neuronal tissues. However, the most significant levels of Papss2 mRNA were found in condensing and proliferating chondrocytes, whereas hypertrophic chondrocytes show a dramatic down-regulation of Papss2 mRNA expression, indicating an important role of the gene product for cartilage growth and development in mouse embryo.