Novel human, mouse and xenopus genes encoding a member of the RAS superfamily of low-molecular-weight GTP-binding proteins and its downregulation in W/W^V mouse jejunum

Background and Aim: Interstitial cells of Cajal (ICC) are pacemakers and mediators of neurotransmission in gastroenteric smooth muscles. Interstitial cells of Cajal require cellular signaling via KIT, a receptor tyrosine kinase, for development and maintenance of cellular phenotype. Much of the evidence demonstrating the functions of ICC comes from studies of W/W^V mutant mice, which have reduced KIT function. The aim of the present study was to differentially examine gene expression in the small intestines of wild-type and W/W^V mice. Methods: RNA from the jejunum of wild-type and W/W ^V mice was analyzed using a differential gene display method. Results: One candidate gene, encoding a novel small GTPase of the RAS superfamily, was significantly suppressed both in fed and starved W/W ^V mice. The full-length clone of the murine gene and its human and xenopus counterparts were designated GTP-binding protein, 28 kDa (G28K). Human G28K cDNA encodes a protein of 258 amino acids with homology to the human cell division cycle 42/G25K protein. This gene is located at 1q42.11-q42.3. G28K was abundantly expressed in the human stomach and the small intestine. Semi-quantitative reverse transcription-polymerase chain reaction analysis revealed expression of G28K mRNA within single isolated ICC. Conclusions: Gene analysis showed that G28K was differentially expressed in the small intestines of wild-type and W/W^V mice. Interstitial cells of Cajal within the small intestine expressed mRNA for G28K. The specific downregulation of G28K in the jejunum of W/W^V mice, and high expression in human intestinal tissue suggest that the G28K gene might be associated with ICC function in mice and in humans.