title: Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia.
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.
authors.affiliation: Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Taketomi
authors.forename: Daigo
authors.initials: D
authors.lastname: Yoshiga
authors.forename: Koji
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nonami
authors.forename: Reiko
authors.initials: R
authors.lastname: Kato
authors.forename: Mika
authors.initials: M
authors.lastname: Sasaki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Sasaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Maiko
authors.initials: M
authors.lastname: Moriyama
authors.forename: Kei-ichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Nishimura
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology*; D004789:Enzyme Activation; D004931:Esophageal Achalasia / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017353:Gene Deletion; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006965:Hyperplasia; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C118389:Spry2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases