CLONING AND EXPRESSION OF MURINE SC1, A GENE-PRODUCT HOMOLOGOUS TO SPARC

A number of cDNAs (SC1, QR1, and hevin) have been shown to be similar to SPARC (secreted protein acidic and rich in cysteine), a matricellul ar protein that regulates cell adhesion, cell cycle, and matrix assemb ly and remodeling. These proteins are 61-65% identical in the final 20 0 residues of their C-termini; their N-terminal sequences are related but more divergent. All have an overall acidic pl, with a follistatin- like region that is rich in cysteine, and a Ca+2 binding consensus seq uence at the C-terminus. Using degenerate primers representing the mos t highly conserved region in SPARC, SC1, and QR1, we identified a 300- BP SC1 clone in a primary polymerase chain reaction (PCR) screen of a mouse brain cDNA library. This cDNA was used to obtain a full-length c lone, which hybridized to a 2.8-KB RNA abundant in brain. Mouse SC1: d isplays a similarity of 70% to mouse SPARC at the amino acid level. No rthern blot and RNAse protection assays revealed a 2.8-KB mRNA express ed at moderate levels (relative to brain) in mouse heart, adrenal glan d, epididymis, and lung, and at low levels in kidney, eye, liver, sple en, submandibular gland, and testis. In contrast to SPARC, in situ hyb ridization showed expression of SC1 mRNA in the tunica media and/or ad ventitia of medium and large vessels; transcripts were not detected in capillaries, venules, or large lymphatics. The distribution of transc ripts for SC1 was also different from that of SPARC in several organs, including adrenal gland, lung, heart, liver, and spleen. Moreover, SC 1 mRNA was not evident in endothelium cultured from rat heart, bovine fetal and adult aorta, mouse aorta, human omentum, and bovine retina. Cultured smooth muscle cells and fibroblasts also failed to express SC 1 mRNA. The absence of SC1 transcript in cultured cells indicates that the SC1 gene is potentially sensitive to regulatory factors in serum or to a three-dimensional architecture conferred by the extracellular matrix that is tacking in vitro. In conclusion, the expression of SPAR C and SC1 appears to be coincident in specific tissues (e.g., adrenal gland and brain), but these proteins exhibit distinct expression patte rns in most organs of the mouse. Because SC1 and SPARC are structurall y similar and exhibit counteradhesive effects on cultured cells, their overlapping and/or adjacent expression in most tissues predicts that one protein might compensate functionally, at least in part, for the o ther. The sequence reported here has been deposited in the GenBank dat a base (accession no. U77330).