Immunocytochemical analyses and targeted gene disruption of GTPBP1

We previously identified a gene encoding a putative GTPase, GTPBP1, which i s structurally related to elongation factor lot, a key component of protein biosynthesis machinery. The primary structure of GTPBP1 is highly conserve d between human and mouse (97% identical at the amino acid level). Expressi on of this gene is enhanced by gamma interferon in a monocytic cell line, T HP-1, Although counterparts of this molecule in Caenorhabditis elegans and Ascaris suum have also been identified, the function of this molecule remai ns to be clarified. In the present study, our immunohistochemical analyses on mouse tissues revealed that GTPBP1 is expressed in some neurons and smoo th muscle cells of various organs as well as macrophages, Immunofluorescenc e analyses revealed that GTPBP1 is localized exclusively in cytoplasm and s hows a diffuse granular network forming a gradient from the nucleus to the periphery of the cells in smooth muscle cell lines and macrophages, To inve stigate the physiological role of GTPBP1, we used targeted gene disruption in embryonic stem cells to generate GTPBP1-deficient mice. The mutant mice were born at the expected Mendelian frequency, developed normally, and were fertile. No manifest anatomical or behavioral abnormality was observed in the mutant mice. Functions of macrophages, including chemotaxis, phagocytos is, and nitric oxide production, in mutant mice were equivalent to those se en in wild-type mice. No significant difference was observed in the immune response to protein antigen between mutant mice and wild-type mice, suggest ing normal function of antigen-presenting cells of the mutant mice. The abs ence of an eminent phenotype in GTPBP1 deficient mice may he due to functio nal compensation by GTPBP2, a molecule we recently identified which is simi lar to GTPBP1 in structure and tissue distribution.