Biology Reference
In-Depth Information
Chapter 22
Model Systems for Studying Kisspeptin
Signalling: Mice and Cells
William H. Colledge , Joanne Doran , and Hua Mei
Abstract 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 signifi cant 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-specifi c expression of
modulator proteins such as the CRE recombinase or fl uorescent reporter proteins
such as GFP allow more sophisticated analyses such as cell or gene ablation or
electrophysiological profi ling. 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.
W. H. Colledge, B.Sc., Ph.D. ( * )
Department of Physiology, Development and Neuroscience, University of Cambridge,
Downing Street , Cambridge, CB2 3EG , UK
e-mail: whc23@cam.ac.uk
J. Doran
Takeda Cambridge , Cambridge , UK
H. Mei
Department of Opthalmology, Cornea Division, University of California,
Los Angeles , CA , USA
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