Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis.
By genetically targeting tumorigenesis to specific hypothalamic neurons in transgenic mice using the promoter region of the gonadotropin-releasing hormone (GnRH) gene to express the SV40 T-antigen oncogene, we have produced neuronal tumors and developed clonal, differentiated, neurosecretory cell lines. These cells extend neurites, express the endogenous mouse GnRH mRNA, release GnRH in response to depolarization, have regulatable fast Na+ channels found in neurons, and express neuronal, but not glial, cell markers. These immortalized cells will provide an invaluable model system for study of hypothalamic neurosecretory neurons that regulate reproduction. Significantly, their derivation demonstrates the feasibility of immortalizing differentiated neurons by targeting tumorigenesis in transgenic mice to specific neurons of the CNS.
Regulatory Biology Laboratory, Salk Institute, La Jolla, California 92037.
P L
PL
Mellon
J J
JJ
Windle
P C
PC
Goldsmith
C A
CA
Padula
J L
JL
Roberts
R I
RI
Weiner
D000818:Animals; D002460:Cell Line; D004563:Electrochemistry; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010906:Pituitary Hormone-Releasing Hormones / Q000235:genetics* / Q000378:metabolism; D013570:Synaptic Membranes / Q000502:physiology; D014407:Tumor Cells, Cultured
D009419:Nerve Tissue Proteins; D010906:Pituitary Hormone-Releasing Hormones