Model systems for studying kisspeptin signalling: mice and cells.

Kisspeptins are a family of overlapping neuropeptides, encoded by the Kiss1 gene, that are required for activation and maintenance of the mammalian reproductive axis. Kisspeptins act within the hypothalamus to stimulate release of gonadotrophic releasing hormone and activation of the pituitary-gonadal axis. Robust model systems are required to dissect the regulatory mechanisms that control Kiss1 neuronal activity and to examine the molecular consequences of kisspeptin signalling. While studies in normal animals have been important in this, transgenic mice with targeted mutations affecting the kisspeptin signalling pathway have played a significant role in extending our understanding of kisspeptin physiology. Knock-out mice recapitulate the reproductive defects associated with mutations in humans and provide an experimentally tractable model system to interrogate regulatory feedback mechanisms. In addition, transgenic mice with cell-specific expression of modulator proteins such as the CRE recombinase or fluorescent reporter proteins such as GFP allow more sophisticated analyses such as cell or gene ablation or electrophysiological profiling. At a less complex level, immortalized cell lines have been useful for studying the role of kisspeptin in cell migration and metastasis and examining the intracellular signalling events associated with kisspeptin signalling.