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Identification and characterization of a novel mouse gene encoding a Ras‐associated guanine nucleotide exchange factor: expression in macrophages and myocarditis elicited by Trypanosoma cruzi parasites

The ability of Trypanosoma cruzi to activate macrophages is, at least in part, attributed to the glycosylphosphatidylinositol‐anchored mucin‐like glycoproteins (GPI‐mucins) expressed in the surface of the trypomastigote stage of the parasite. The differential display reverse transcriptase‐polymerase chain reaction and the reverse Northern blot were used to study modulation of gene expression in murine macrophages exposed to GPI‐mucins and in cardiac tissues from mice infected with T. cruzi. Among several cDNAs that were more abundant in lanes corresponding to macrophages stimulated with GPI‐mucins as compared with resting cells, we confirmed the differential expression of A1, interleukin‐18, and GPIγ4. Some of these genes were also shown to have enhanced expression in the cardiac tissue (DAP‐12, A1, and GPIγ4) from infected animals. The expression of GPIγ4 was also enhanced in human monocytes stimulated with GPI‐mucins or bacterial lipopolysaccharides. The complete sequence of the GPIγ4 transcript and its gene including the 5′ upstream region was defined. GPIγ4 was encoded by a novel, single copy gene present in mouse as well as human genomes and showed conserved homology to different members of the guanine nucleotide exchange factor family.