Visualisation of Kiss1 Neurone Distribution Using a Kiss1-CRE Transgenic Mouse.
Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE-GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss-CRE heterozygous mice with CRE-activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80-90% of tdTomato positive neurones in the ARC were co-labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato-labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several hypothalamic regions, including rostrally to the periventricular and pre-optic areas and to the lateral hypothalamus.
Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
S-H
SH
Yeo
Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
V
V
Kyle
Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
P G
PG
Morris
Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
S
S
Jackman
Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
L C
LC
Sinnett-Smith
Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
M
M
Schacker
School of Biomedical Sciences, University of Queensland, St Lucia, Australia.
C
C
Chen
Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
W H
WH
Colledge
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology* / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D005260:Female; D005835:Genitalia / Q000378:metabolism; D007032:Hypothalamus, Anterior / Q000166:cytology* / Q000378:metabolism*; D007246:Infertility / Q000235:genetics; D059648:Kisspeptins / Q000032:analysis* / Q000235:genetics; D008297:Male; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009929:Organ Size; D012741:Sexual Maturation / Q000235:genetics
C491407:Kiss1 protein, mouse; D059648:Kisspeptins

CLARITY
; Kiss-CRE; mouse; neuronal distribution; tdTomato; transgenic
Neuroscience. 2011 Jan 26;173:37-56
21093546
Reproduction. 2011 Mar;141(3):357-66
21156837
Endocrinology. 2015 Jul;156(7):2582-94
25856430
FASEB J. 2008 Aug;22(8):2676-89
18390925
Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22693-8
21149719
Endocrinology. 2013 Dec;154(12):4939-45
24092638
Adv Exp Med Biol. 2013;784:481-503
23550020
J Clin Endocrinol Metab. 1996 Oct;81(10):3654-62
8855818
Endocrinology. 2011 Nov;152(11):4298-309
21933870
Endocrinology. 2012 Nov;153(11):5384-93
22989626
Brain Res. 2010 Dec 10;1364:129-38
20800054
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):1027-32
17209010
Endocrinology. 2007 Oct;148(10):4927-36
17595229
J Neurosci. 2008 Aug 27;28(35):8691-7
18753370
Endocrinology. 2005 Jul;146(7):2976-84
15831567
J Neuroendocrinol. 2009 Aug;21(8):673-82
19515163
Endocrinology. 2011 Mar;152(3):1001-12
21239443
Nat Methods. 2013 Jun;10(6):508-13
23722210
Neuroendocrinology. 2016 Apr 8;:null
27054958
Endocrinology. 2011 May;152(5):2020-30
21363930
Endocr Rev. 2009 Oct;30(6):713-43
19770291
Peptides. 2009 Jan;30(1):34-41
18571287
Endocrinology. 2005 Oct;146(10):4431-6
15976058
Cold Spring Harb Protoc. 2012 Sep 01;2012(9):969-83
22949711
J Neurosci. 2005 Dec 7;25(49):11349-56
16339030
J Neuroendocrinol. 2013 Sep;25(9):839-51
23822722
Peptides. 2009 Jan;30(1):154-63
18838092
Endocrinology. 2011 Jun;152(6):2387-99
21486932
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10714-9
17563351