The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system.
GPR54 is a G-protein-coupled receptor that displays a high percentage of identity in the transmembrane domains with the galanin receptors. The ligand for GPR54 has been identified as a peptide derived from the KiSS-1 gene. KiSS-1 has been shown to have anti-metastatic effects, suggesting that KiSS-1 or its receptor represents a potential therapeutic target. To further our understanding of the physiological function of this receptor, we have generated a mutant mouse line with a targeted disruption of the GPR54 receptor (GPR54 -/-). The analysis of the GPR54 mutant mice revealed developmental abnormalities of both male and female genitalia and histopathological changes in tissues which normally contain sexually dimorphic features. These data suggest a role for GPR54/KiSS-1 in normal sexual development, and indicate that study of the GPR54 mutant mice may provide valuable insights into human reproductive syndromes.
Funes
Sandrine
S
Functional Genomics Research, Discovery Technologies Department, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
Hedrick
Joseph A
JA
Vassileva
Galya
G
Markowitz
Lisa
L
Abbondanzo
Susan
S
Golovko
Andrei
A
Yang
Shijun
S
Monsma
Frederick J
FJ
Gustafson
Eric L
EL
D000818:Animals; D005260:Female; D005835:Genitalia / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D007006:Hypogonadism / Q000473:pathology / Q000503:physiopathology; D059648:Kisspeptins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009928:Organ Specificity; D010641:Phenotype; D011506:Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide / Q000172:deficiency / Q000378:metabolism*; D012098:Reproduction / Q000502:physiology*; D012741:Sexual Maturation / Q000502:physiology*; D014018:Tissue Distribution
C491407:Kiss1 protein, mouse; C492248:Kiss1r protein, mouse; D059648:Kisspeptins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide