Ncx (Enx, Hox11L.1) is required for neuronal cell death in enteric ganglia of mice.
OBJECTIVE
Ncx (Enx, Hox11L.1)-deficient (Ncx-/-) mice develop mega-ileo-ceco-colon with a larger number of neuronal cells in the enteric ganglia. We investigated mechanisms related to this abnormality and directed our attention to the effects on gastrointestinal tract functions.


METHODS
The number of NADPH diaphorase or cuprolinic blue-positive neuronal cells in the enteric ganglia was examined during growth of the mice. Neuronal cell death of enteric ganglia was assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling. Function of the gastrointestinal tract was determined by measuring excretion time of the barium chloride given into the stomach.


RESULTS
The number of neuronal cells decreased in control mice older than 2 weeks, and neuronal cell death was evident in the ganglia. However, the number of neuronal cells did not decrease in Ncx-/- mice, and cell death was rare. Excretion time of barium chloride was prolonged in all Ncx-/- mice examined and was improved by the administration of an inhibitor of nitric oxide synthase.


CONCLUSIONS
Ncx participates in cell death of enteric neurons. Motor abnormality of the gastrointestinal tract in Ncx-/- mice may be attributed to the large number of neuronal cells.
Aoki
Taito
T
Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Chuo-ku, Chiba city, Chiba 260-8670, Japan.
Jusuf
Ahmad Aulia
AA
Iitsuka
Yoshinuri
Y
Isono
Kaichi
K
Tokuhisa
Takeshi
T
Hatano
Masahiko
M
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D017209:Apoptosis / Q000235:genetics*; D017609:Barium Compounds / Q000493:pharmacokinetics; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D002452:Cell Count; D019070:Cell Lineage; D002465:Cell Movement; D002712:Chlorides / Q000493:pharmacokinetics; D004396:Coloring Agents / Q000032:analysis; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000254:growth & development / Q000473:pathology*; D004790:Enzyme Induction; D005772:Gastrointestinal Transit / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D019254:Genes, bcl-2; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000032:analysis; D007421:Intestine, Small / Q000254:growth & development / Q000294:innervation; D008531:Megacolon / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009252:NADPH Dehydrogenase / Q000032:analysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use; D009432:Neural Crest / Q000166:cytology; D009474:Neurons / Q000473:pathology*; D009942:Organometallic Compounds / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013194:Staining and Labeling; D013270:Stomach / Q000254:growth & development / Q000294:innervation
D017609:Barium Compounds; D002712:Chlorides; D004396:Coloring Agents; D018398:Homeodomain Proteins; D007211:Indoles; D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; C107836:Tlx2 protein, mouse; C024986:barium chloride; C015445:copper phthalocyanine; D009252:NADPH Dehydrogenase; D053148:Caspase 3; D019331:NG-Nitroarginine Methyl Ester