Characterization of Kiss1 neurons using transgenic mouse models

R. M. Cravo, L. O. Margatho, S. Osborne-Lawrence, J. Donato, S. Atkin, A. L. Bookout, S. Rovinsky, R. Frazão, C. E. Lee, L. Gautron, J. M. Zigman, C. F. Elias

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Abstract

Humans and mice with loss-of-function mutations of the genes encoding kisspeptins (Kiss1) or kisspeptin receptor (Kiss1r) are infertile due to hypogonadotropic hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In order to better study the different populations of kisspeptin cells we generated Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre-dependent expression of green fluorescent protein or β-galactosidase. Also, we demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the Arc and higher leptin-responsivity was observed in the most caudal population of Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons was observed. Melanocortin fibers innervated subsets of Kiss1 neurons of the preoptic area and Arc, and both populations expressed melanocortin receptors type 4 (MC4R). Specifically in the preoptic area, 18-28% of Kiss1 neurons expressed MC4R. In the Arc, 90% of Kiss1 neurons were glutamatergic, 50% of which also were GABAergic. In the AVPV, 20% of Kiss1 neurons were glutamatergic whereas 75% were GABAergic. The differences observed between the Kiss1 neurons in the preoptic area and the Arc likely represent neuronal evidence for their differential roles in metabolism and reproduction.

Original languageEnglish (US)
Pages (from-to)37-56
Number of pages20
JournalNeuroscience
Volume173
DOIs
StatePublished - Jan 26 2011

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Transgenic Mice
Neurons
Preoptic Area
Kisspeptins
Anterior Hypothalamus
Leptin
Receptor, Melanocortin, Type 4
Galactosidases
Anterior Thalamic Nuclei
Melanocortins
Population
Messenger RNA
Arcuate Nucleus of Hypothalamus
Hypogonadism
Green Fluorescent Proteins
Cerebral Cortex
Hypothalamus
Reproduction
Mutation
Genes

Keywords

  • Cre-recombinase
  • GAD-67
  • Leptin
  • Melanocortin
  • Reporter mouse
  • VGluT2

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cravo, R. M., Margatho, L. O., Osborne-Lawrence, S., Donato, J., Atkin, S., Bookout, A. L., ... Elias, C. F. (2011). Characterization of Kiss1 neurons using transgenic mouse models. Neuroscience, 173, 37-56. https://doi.org/10.1016/j.neuroscience.2010.11.022

Characterization of Kiss1 neurons using transgenic mouse models. / Cravo, R. M.; Margatho, L. O.; Osborne-Lawrence, S.; Donato, J.; Atkin, S.; Bookout, A. L.; Rovinsky, S.; Frazão, R.; Lee, C. E.; Gautron, L.; Zigman, J. M.; Elias, C. F.

In: Neuroscience, Vol. 173, 26.01.2011, p. 37-56.

Research output: Contribution to journalArticle

Cravo, RM, Margatho, LO, Osborne-Lawrence, S, Donato, J, Atkin, S, Bookout, AL, Rovinsky, S, Frazão, R, Lee, CE, Gautron, L, Zigman, JM & Elias, CF 2011, 'Characterization of Kiss1 neurons using transgenic mouse models', Neuroscience, vol. 173, pp. 37-56. https://doi.org/10.1016/j.neuroscience.2010.11.022
Cravo RM, Margatho LO, Osborne-Lawrence S, Donato J, Atkin S, Bookout AL et al. Characterization of Kiss1 neurons using transgenic mouse models. Neuroscience. 2011 Jan 26;173:37-56. https://doi.org/10.1016/j.neuroscience.2010.11.022
Cravo, R. M. ; Margatho, L. O. ; Osborne-Lawrence, S. ; Donato, J. ; Atkin, S. ; Bookout, A. L. ; Rovinsky, S. ; Frazão, R. ; Lee, C. E. ; Gautron, L. ; Zigman, J. M. ; Elias, C. F. / Characterization of Kiss1 neurons using transgenic mouse models. In: Neuroscience. 2011 ; Vol. 173. pp. 37-56.
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abstract = "Humans and mice with loss-of-function mutations of the genes encoding kisspeptins (Kiss1) or kisspeptin receptor (Kiss1r) are infertile due to hypogonadotropic hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In order to better study the different populations of kisspeptin cells we generated Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre-dependent expression of green fluorescent protein or β-galactosidase. Also, we demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the Arc and higher leptin-responsivity was observed in the most caudal population of Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons was observed. Melanocortin fibers innervated subsets of Kiss1 neurons of the preoptic area and Arc, and both populations expressed melanocortin receptors type 4 (MC4R). Specifically in the preoptic area, 18-28{\%} of Kiss1 neurons expressed MC4R. In the Arc, 90{\%} of Kiss1 neurons were glutamatergic, 50{\%} of which also were GABAergic. In the AVPV, 20{\%} of Kiss1 neurons were glutamatergic whereas 75{\%} were GABAergic. The differences observed between the Kiss1 neurons in the preoptic area and the Arc likely represent neuronal evidence for their differential roles in metabolism and reproduction.",
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AU - Atkin, S.

AU - Bookout, A. L.

AU - Rovinsky, S.

AU - Frazão, R.

AU - Lee, C. E.

AU - Gautron, L.

AU - Zigman, J. M.

AU - Elias, C. F.

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