Ncx (Enx, Hox11L.1) is required for neuronal cell death in enteric ganglia of mice

J Pediatr Surg. 2007 Jun;42(6):1081-8. doi: 10.1016/j.jpedsurg.2007.01.064.

Abstract

Background/purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Animals, Suckling
  • Apoptosis / genetics*
  • Barium Compounds / pharmacokinetics
  • Caspase 3 / biosynthesis
  • Caspase 3 / genetics
  • Cell Count
  • Cell Lineage
  • Cell Movement
  • Chlorides / pharmacokinetics
  • Coloring Agents / analysis
  • Disease Models, Animal
  • Enteric Nervous System / growth & development
  • Enteric Nervous System / pathology*
  • Enzyme Induction
  • Gastrointestinal Transit / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Genes, bcl-2
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • In Situ Nick-End Labeling
  • Indoles / analysis
  • Intestine, Small / growth & development
  • Intestine, Small / innervation
  • Megacolon / genetics*
  • Megacolon / pathology
  • Mice
  • Mice, Knockout
  • NADPH Dehydrogenase / analysis
  • NG-Nitroarginine Methyl Ester / pharmacology
  • NG-Nitroarginine Methyl Ester / therapeutic use
  • Neural Crest / cytology
  • Neurons / pathology*
  • Organometallic Compounds / analysis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Staining and Labeling
  • Stomach / growth & development
  • Stomach / innervation

Substances

  • Barium Compounds
  • Chlorides
  • Coloring Agents
  • Homeodomain Proteins
  • Indoles
  • Organometallic Compounds
  • Proto-Oncogene Proteins c-bcl-2
  • Tlx2 protein, mouse
  • barium chloride
  • copper phthalocyanine
  • NADPH Dehydrogenase
  • Caspase 3
  • NG-Nitroarginine Methyl Ester