Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia

Nat Neurosci. 2005 Jul;8(7):855-7. doi: 10.1038/nn1485.

Abstract

We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction. Glial cell line-derived neurotrophic factor (GDNF) induced hyperactivation of ERK and Akt in enteric nerve cells. Anti-GDNF antibody administration corrected nerve hyperplasia in Sprouty2-deficient mice. We show Sprouty2 to be a negative regulator of GDNF for the neonatal development or survival of enteric nerve cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antibodies / pharmacology
  • Enteric Nervous System / metabolism
  • Enteric Nervous System / pathology*
  • Enzyme Activation
  • Esophageal Achalasia / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Deletion*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Hyperplasia
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Nerve Growth Factors / immunology
  • Nerve Growth Factors / metabolism*
  • Neurons / pathology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteins / genetics*
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies
  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Growth Factors
  • Proteins
  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Spry2 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases