Targeted disruption of the neuronal nitric oxide synthase gene

Cell. 1993 Dec 31;75(7):1273-86. doi: 10.1016/0092-8674(93)90615-w.


By homologous recombination, we have generated mice that lack the neuronal nitric oxide synthase (NOS) gene. Neuronal NOS expression and NADPH-diaphorase (NDP) staining are absent in the mutant mice. Very low level residual catalytic activity suggests that other enzymes in the brain may generate nitric oxide. The neurons normally expressing NOS appear intact, and the mutant NOS mice are viable, fertile, and without evident histopathological abnormalities in the central nervous system. The most evident effect of disrupting the neuronal NOS gene is the development of grossly enlarged stomachs, with hypertrophy of the pyloric sphincter and the circular muscle layer. This phenotype resembles the human disorder infantile pyloric stenosis, in which gastric outlet obstruction is associated with the lack of NDP neurons in the pylorus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / genetics*
  • Amino Acid Oxidoreductases / metabolism
  • Animals
  • Brain / anatomy & histology
  • Brain / enzymology
  • Brain Mapping
  • Cloning, Molecular
  • Gene Expression
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / enzymology*
  • Nitric Oxide Synthase
  • Pyloric Stenosis / enzymology
  • Pyloric Stenosis / pathology
  • RNA, Messenger / genetics
  • Stomach / anatomy & histology


  • RNA, Messenger
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases