Figure 1.

spCSF-1, but not csCSF-1, contributes to the increase in serum CSF-1, and both are upregulated in the kidney with advancing disease in MRL-Fas^lpr mice. (A) CSF-1 isoform transgenes driven by Csf1 promoter (3.13 kb) and first intron (3.28 kb). TgC contains the full-length cDNA (exons 1 to 9). The other transgenes are altered as follows. Both TgSPP and TgSGP contain a stop codon at amino acid 456 to ensure that they are secreted. TgSGP has, in addition, a mutation (S276L-G277A) in the unique glycosaminoglycan (GAG) addition site (SGXG/A) to prevent addition of the chondroitin sulfate chain. csCSF-1, incorporated in TgCS results from alternative splicing in exon 6 that removes the GAG addition site and sequences encoding the proteolytic cleavage sites that release the secreted forms from their transmembrane tether (reviewed in reference ¹²). (B) Serum and kidney CSF-1 levels in TgC/+, TgCS/+, TgSPP/+, and TgSGP/+ mice with advancing lupus nephritis (1.5, 3.0, and 5.0 months of age); MRL-Fas^lpr mice (WT, wild type) and Csf1^op/op mice served as controls. CSF-1 levels in serum and in kidney homogenates determined by ELISA. The values are the means ± SEM.