Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia.
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.
Taketomi
Takaharu
T
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Yoshiga
Daigo
D
Taniguchi
Koji
K
Kobayashi
Takashi
T
Nonami
Atsushi
A
Kato
Reiko
R
Sasaki
Mika
M
Sasaki
Atsuo
A
Ishibashi
Hitoshi
H
Moriyama
Maiko
M
Nakamura
Kei-ichiro
K
Nishimura
Junji
J
Yoshimura
Akihiko
A
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
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