W(sh)/W(sh) c-Kit mutant mice possess interstitial cells of Cajal in the deep muscular plexus layer of the small intestine.
The c-Kit receptor tyrosine kinase regulates the development and differentiation of various progenitor cells. W mutant mice with spontaneous mutations in the c-kit gene show various phenotypes such as anemia, infertility, loss of coat color and mast cells. c-Kit also regulates the development of the interstitial cells of Cajal (ICC) that are responsible for the motility regulation of the gastrointestinal musculature. W(sh)/W(sh) mice possess an inversion mutation upstream of the c-kit promoter region; this mutation is responsible for reducing c-Kit activity, leading to a decrease in the number of mast cells, melanocytes, and ICC. We extensively examined the small intestine of W(sh)/W(sh) mice by using immunohistochemistry and electron microscopy. Although the musculature of the W(sh)/W(sh) mice did not show any c-Kit immunoreactivity, there were neurokinin 1 receptor (NK1R)-immunopositive cells that were associated with the nerve fibers in the deep muscular plexus (DMP) region. These NK1R-immunopositive cells showed a bipolar shape with long processes and were identified as ICC in the DMP layer (ICC-DMP). Electron microscopic analysis revealed that ICC-DMP had numerous mitochondria, caveolae, and gap junctions and were closely associated with nerve terminals. In contrast, ICC were not observed at the myenteric layer. In the small intestine of the W(sh)/W(sh) mice, we detected ICC-DMP that showed NK1R immunoreactivity and ultrastructural characters. This type of ICC may develop and maturate structurally without c-Kit expression and regulate gastrointestinal motility.
Iino
Satoshi
S
Department of Morphological and Physiological Sciences, University of Fukui, Faculty of Medical Sciences, Matsuoka, Eiheiji, Fukui 910-1193, Japan. iinosa@u-fukui.ac.jp
Horiguchi
Kazuhide
K
Nojyo
Yoshiaki
Y
D000818:Animals; D021941:Caveolae / Q000648:ultrastructure; D054351:Electrical Synapses / Q000648:ultrastructure; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism
D018040:Receptors, Neurokinin-1; D019009:Proto-Oncogene Proteins c-kit