Requirement of c-kit for development of intestinal pacemaker system.
A discovery that the protooncogene encoding the receptor tyrosine kinase, c-kit, is allelic with the Dominant white spotting (W) locus establishes that c-kit plays a functional role in the development of three cell lineages, melanocyte, germ cell, and hematopoietic cell which are defective in W mutant mice. Recent analyses of c-kit expression in various tissues of mouse, however, have demonstrated that c-kit is expressed in more diverse tissues which are phenotypically normal in W mutant mice. Thus, whether or not c-kit expressed outside the three known cell lineages plays a functional role is one of the important questions needing answering in order to fully elucidate the role of c-kit in the development of the mouse. Here, we report that some of the cells in smooth muscle layers of developing intestine express c-kit. Blockade of its function for a few days postnatally by an antagonistic anti-c-kit monoclonal antibody (mAb) results in a severe anomaly of gut movement, which in BALB/c mice produces a lethal paralytic ileus. Physiological analysis indicates that the mechanisms required for the autonomic pacing of contraction in an isolated gut segment are defective in the anti-c-kit mAb-treated mice, W/Wv mice and even W/+ mice. These findings suggest that c-kit plays a crucial role in the development of a component of the pacemaker system that is required for the generation of autonomic gut motility.
Maeda
H
H
Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
Yamagata
A
A
Nishikawa
S
S
Yoshinaga
K
K
Kobayashi
S
S
Nishi
K
K
Nishikawa
S
S
D000818:Animals; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005769:Gastrointestinal Motility / Q000235:genetics*; D007422:Intestines / Q000196:embryology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000196:embryology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit