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/WV mouse jejunum.
OBJECTIVE
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/WV 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.
Daigo
Yataro
Y
Department of Medicine, University of Yamanashi School of Medicine, Yamanashi, Japan.
Takayama
Ichiro
I
Ponder
Bruce A J
BA
Caldas
Carlos
C
Ward
Sean M
SM
Sanders
Kenton M
KM
Fujino
Masayuki A
MA
D000818:Animals; D020558:GTP Phosphohydrolases / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005769:Gastrointestinal Motility; D020869:Gene Expression Profiling; D006801:Humans; D007583:Jejunum / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013217:Starvation; D014981:Xenopus; D020764:cdc42 GTP-Binding Protein / Q000235:genetics
D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D020764:cdc42 GTP-Binding Protein