Intestinal neuronal dysplasia-like pathology in Ncx/Hox11L.1 gene-deficient mice.
OBJECTIVE
Ncx/Hox11L.1-deficient (Ncx-/-) mice specifically created by the authors had mega-ileo-ceco-colon (mega-ICC) with a caliber change in the proximal colon. The authors studied the nerve distribution in the bowel of these Ncx-/- mice to determine the cause of their bowel dysmotility.


METHODS
Four-week-old Ncx-/- mice (n = 10; 5 with mega-ICC, 5 without mega-ICC) were killed and the bowel harvested. Half of each specimen was snap frozen for AchE and NADPH-diaphorase histochemistry, and the other half were fixed with 10% formalin for H&E staining and immunohistochemistry using PGP9.5 antibody (a marker for neurons), C-kit antibody (a marker for intestinal pacemaker cells), and stem cell factor antibody (a marker for C-kit ligand). Age-matched wild-type normal mice (n = 5) served as controls.


RESULTS
In the ileum, cecum, and proximal colon from all Ncx-/- mice (irrespective of the association of mega-ICC), typical findings of human intestinal neuronal dysplasia (IND) ie, obvious hyperganglionosis in neuronal plexuses on PGP9.5 immunohistochemistry, ectopic ganglia in the mucosal and muscular layers on AchE histochemistry, and ghostlike ganglia on NADPH-diaphorase histochemistry were found. Likewise, in normal caliber distal colon from these mice, the distribution of ganglion cells, C-kit, and stem cell factor was normal. In control specimens, there was no ectopic ganglia or hyperganglionosis.


CONCLUSIONS
These findings suggest that the Ncx/Hox11L.1 gene is required for the proper innervation of the enteric nervous system in mice, and our deficient strain may be useful as a model for studying IND in humans.
Yamataka
A
A
Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Hatano
M
M
Kobayashi
H
H
Wang
K
K
Miyahara
K
K
Sueyoshi
N
N
Miyano
T
T
D000818:Animals; D003106:Colon / Q000294:innervation* / Q000473:pathology*; D003108:Colonic Diseases / Q000235:genetics* / Q000473:pathology; D046508:Culture Techniques; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000473:pathology*; D005724:Ganglia / Q000473:pathology / Q000502:physiology; D005769:Gastrointestinal Motility / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000032:analysis; D015513:Oncogene Proteins / Q000235:genetics*; D012016:Reference Values; D012680:Sensitivity and Specificity
D018398:Homeodomain Proteins; D009478:Neuropeptide Y; D015513:Oncogene Proteins; C487378:Tlx1 protein, mouse