The gene encoding GnRH and its associated peptide GAP: some insights into hypogonadism.
The hypogonadal (hpg) mouse represents a unique animal model for hypogonadism. In this mutant the truncation of the gene encoding GnRH and its associated peptide GAP leads to drastically lowered gonadotropin levels and increased circulating prolactin. This deficiency in turn leads to a failure of testes and ovaries to develop normally. Using gene therapy we have restored the reproductive functions of the hpg mouse. The success of this therapy uniquely underscores the importance of the gene encoding the GnRH precursor and lends credence to the hypothesis that no other gene in mammals can replace it. As a consequence, defects in the control and/or structural properties of the human GnRH are expected to result in hypogonadism in humans.
Seeburg
P H
PH
Genentech Inc, South San Francisco, CA 94080.
Mason
A J
AJ
Young
W S
WS
Stewart
T A
TA
Nikolics
K
K
D000595:Amino Acid Sequence; D000818:Animals; D015316:Genetic Therapy; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006065:Gonadotropins, Pituitary / Q000032:analysis; D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009929:Organ Size; D010906:Pituitary Hormone-Releasing Hormones / Q000235:genetics*; D011388:Prolactin / Q000032:analysis; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D015183:Restriction Mapping
D006065:Gonadotropins, Pituitary; D010906:Pituitary Hormone-Releasing Hormones; D011498:Protein Precursors; C050502:gonadotropin releasing hormone associated peptide; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin