Renal and neuronal abnormalities in mice lacking GDNF.
Glial cell-line derived neurotrophic factor (GDNF) is a potent survival factor for embryonic midbrain dopaminergic, spinal motor, cranial sensory, sympathetic, and hindbrain noradrenergic neurons, and is available to these cells in vivo. It is therefore considered a physiological trophic factor and a potential therapeutic agent for Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Here we show that at postnatal day 0 (P0), GDNF-deficient mice have deficits in dorsal root ganglion, sympathetic and nodose neurons, but not in hindbrain noradrenergic or midbrain dopaminergic neurons. These mice completely lack the enteric nervous system (ENS), ureters and kidneys. Thus GDNF is important for the development and/or survival of enteric, sympathetic and sensory neurons and the renal system, but is not essential for catecholaminergic neurons in the central nervous system (CNS).
Moore
M W
MW
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080, USA.
Klein
R D
RD
Fariñas
I
I
Sauer
H
H
Armanini
M
M
Phillips
H
H
Reichardt
L F
LF
Ryan
A M
AM
Carver-Moore
K
K
Rosenthal
A
A
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D004064:Digestive System / Q000196:embryology* / Q000294:innervation; D004065:Digestive System Abnormalities; D004298:Dopamine / Q000378:metabolism; D018390:Gene Targeting; D051100:Glial Cell Line-Derived Neurotrophic Factor; D017403:In Situ Hybridization; D007668:Kidney / Q000002:abnormalities / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000166:cytology; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014513:Ureter / Q000196:embryology
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D004298:Dopamine