The mechanism of intestinal motility in homozygous mutant Ncx/Hox11L.1-deficient mice--a model for intestinal neuronal dysplasia.
OBJECTIVE
Homozygous mutant Ncx/Hox11L.1-deficient (Ncx-/-) mice develop mega-ileo-ceco-colon with a caliber change in the proximal colon. This study investigated the mechanism of intestinal motility in these mice.


METHODS
Five-week-old male and female Ncx-/- mice with mega-ileo-ceco-colon (n = 8) were compared with age-matched male BDF1 mice used as controls (n = 8). All mice were sacrificed, and uniform-sized strips of jejunum, ileum, proximal colon, and distal colon were exposed to electrical field stimulation and pretreatment with atropine sulfate, guanethidine, or tetrodotoxin. Contractile responses were recorded and compared.


RESULTS
Longitudinal muscle from strips of jejunum and ileum from all mice (BDF1 and Ncx-/-) did not respond to electrical field stimulation, whereas ileal circular muscle contracted in BDF1 mice and contracted and relaxed in Ncx-/- mice. Pretreatment with atropine sulfate and guanethidine inhibited the responses of circular muscle of distal colon and ileum in BDF1 mice significantly (P < .05), but no effect was observed in Ncx-/- mice.


CONCLUSIONS
In ileum, BDF1 mice have cholinergic and adrenergic dominant contraction patterns, whereas Ncx-/- mice have relaxation-dominant patterns because of nonadrenergic, noncholinergic nerves. Based on this, there would appear to be some kind of variation in the gastrointestinal nerve supply in Ncx-/- mice.
Kobayashi
Hiroyuki
H
Department of General Medicine and Hospital Administration, Juntendo University School of Medicine, Tokyo 113-8421, Japan. koba@med.juntendo.ac.jp
Kusafuka
Junichi
J
Lane
Geoffrey J
GJ
Yamataka
Atsuyuki
A
Satoh
Kazuko
K
Hayakawa
Terumasa
T
Kase
Yoshio
Y
Hatano
Masahiko
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000473:pathology*; D005260:Female; D005724:Ganglia / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006627:Hirschsprung Disease / Q000503:physiopathology; D018398:Homeodomain Proteins; D007410:Intestinal Diseases / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation* / Q000502:physiology; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013368:Submucous Plexus / Q000502:physiology
D018398:Homeodomain Proteins; C107836:Tlx2 protein, mouse; D000109:Acetylcholine