RENAL AND NEURONAL ABNORMALITIES IN MICE LACKING GDNF

GLIAL cell-line derived neurotrophic factor (GDNF) is a potent surviva l factor for embryonic midbrain dopaminergic(1), spinal motor(2), cran ial sensory(3), sympathetic, and hindbrain noradrenergic(4) neurons, a nd is available to these cells in vivo. It is therefore considered a p hysiological trophic factor and a potential therapeutic agent for Park inson's disease(5,6), amyotrophic lateral sclerosis(7), and Alzheimer' s disease(4). Here we show that at postnatal day 0 (P0), GDNF-deficien t mice have deficits in dorsal root ganglion, sympathetic and nodose n eurons, but not in hindbrain noradrenergic or midbrain dopaminergic ne urons. These mice completely lack the enteric nervous system (ENS), ur eters and kidneys. Thus GDNF is important for the development and/or s urvival of enteric, sympathetic and sensory neurons and the renal syst em, but is not essential for catecholaminergic neurons in the central nervous system (CNS).