title: Characterization of Kiss1 neurons using transgenic mouse models.
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.
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard Dallas, TX, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Cravo
authors.forename: L O
authors.initials: LO
authors.lastname: Margatho
authors.forename: S
authors.initials: S
authors.lastname: Osborne-Lawrence
authors.forename: J
authors.initials: J
authors.lastname: Donato
authors.forename: S
authors.initials: S
authors.lastname: Atkin
authors.forename: A L
authors.initials: AL
authors.lastname: Bookout
authors.forename: S
authors.initials: S
authors.lastname: Rovinsky
authors.forename: R
authors.initials: R
authors.lastname: Frazão
authors.forename: C E
authors.initials: CE
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Gautron
authors.forename: J M
authors.initials: JM
authors.lastname: Zigman
authors.forename: C F
authors.initials: CF
authors.lastname: Elias
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D059648:Kisspeptins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D011506:Proteins