Migratory arrest of gonadotropin-releasing hormone neurons in transgenic mice.
Gonadotropin-releasing hormone (GnRH) is important in reproduction, although the mechanism of central hypogonadism in humans remains unclear. Because the GnRH neuron originates from the olfactory placode and migrates to the hypothalamus during development, central hypogonadism in humans could be caused by failure in normal migration of GnRH neurons to the hypothalamus. We report that in transgenic mice expression of the simian virus 40 T antigen, driven by the promoter of human GnRH gene, resulted in central hypogonadism due to an arrest in neuronal migration during development and tumor formation along the migratory pathway. This system appears to be an important animal model of hypogonadotropic hypogonadism in humans. Additionally, olfactory bulb tumors from these animals were dispersed, and a GnRH-secreting neuronal cell line (GN cell line) was established.
Radovick
S
S
Department of Pediatrics, University Hospitals of Cleveland, Case Western Reserve University, OH 44106.
Wray
S
S
Lee
E
E
Nicols
D K
DK
Nakayama
Y
Y
Weintraub
B D
BD
Westphal
H
H
Cutler
G B
GB
Wondisford
F E
FE
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D007006:Hypogonadism / Q000235:genetics* / Q000473:pathology; D007031:Hypothalamus / Q000166:cytology; D007247:Infertility, Female; D007248:Infertility, Male; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009481:Neurophysins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins
D000952:Antigens, Polyomavirus Transforming; D009481:Neurophysins; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone