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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antibodies / pharmacology
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Enteric Nervous System / metabolism
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Enteric Nervous System / pathology*
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Enzyme Activation
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Esophageal Achalasia / genetics*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Deletion*
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Glial Cell Line-Derived Neurotrophic Factor
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Hyperplasia
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Mice
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Mice, Knockout
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Nerve Growth Factors / immunology
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Nerve Growth Factors / metabolism*
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Neurons / pathology*
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Protein Serine-Threonine Kinases / metabolism
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Proteins / genetics*
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Proteins / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
Substances
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Adaptor Proteins, Signal Transducing
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Antibodies
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Gdnf protein, mouse
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Glial Cell Line-Derived Neurotrophic Factor
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Growth Factors
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Proteins
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Proto-Oncogene Proteins
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Spry2 protein, mouse
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Extracellular Signal-Regulated MAP Kinases