PMID- 32470472 OWN - NLM STAT- MEDLINE DCOM- 20201218 LR - 20201218 IS - 1095-6840 (Electronic) IS - 0016-6480 (Linking) VI - 295 DP - 2020 Sep 1 TI - Ectopic over expression of kiss1 may compensate for the loss of kiss2. PG - 113523 LID - S0016-6480(20)30276-8 [pii] LID - 10.1016/j.ygcen.2020.113523 [doi] AB - Kisspeptin (KISS) is a neuropeptide which plays a central role in the regulation of the hypothalamic-pituitary-gonadal axis, and is essential for sexual maturation and fertility in mammals. Unlike mammals, which possess only one KISS gene, two paralogous genes, kiss1 and kiss2, have been identified in zebrafish and other non-mammalian vertebrates. Previous studies suggest that Kiss2, but not Kiss1, is the reproduction relevant form amongst the two. To better understand the role of each of these isoforms in reproduction, a loss of function approach was applied. Two genetic manipulation techniques-clustered regularly interspaced short palindromic repeats (CRISPR) and transcription activator-like effector nucleases (TALEN)-were used to generate kiss1 and kiss2 knockout (KO) zebrafish lines, respectively. Examination of these KO lines showed that reproductive capability was not impaired, confirming earlier observations. Further analysis revealed that KO of kiss2 caused a significant increase in expression levels of kiss1, kiss2r and tac3a, while KO of kiss1 had no effect on the expression of any of the examined genes. In situ hybridization analysis revealed that kiss1 mRNA is expressed only in the habenula in wild type brains, while in kiss2 KO fish, kiss1 mRNA-expressing cells were identified also in the ventral telencephalon, the ventral part of the entopeduncular nucleus, and the dorsal and ventral hypothalamus. Interestingly, these regions are known to express kiss2r, and the ventral hypothalamus normally expresses kiss2. These results suggest that a compensatory mechanism, involving ectopic kiss1 expression, takes place in the kiss2 KO fish, which may substitute for Kiss2 activity. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Etzion, Talya AU - Etzion T AD - Department of Neurobiology, George S. Wise Faculty of Life Sciences and Sagol School of Neurosciences, University of Tel Aviv, Tel Aviv 69978, Israel. FAU - Zmora, Nilli AU - Zmora N AD - Department of Marine Biotechnology, Institute of Marine and Environmental Technology, University of Maryland Baltimore County, Baltimore, MD, USA. FAU - Zohar, Yonatan AU - Zohar Y AD - Department of Marine Biotechnology, Institute of Marine and Environmental Technology, University of Maryland Baltimore County, Baltimore, MD, USA. FAU - Levavi-Sivan, Berta AU - Levavi-Sivan B AD - Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot 76100, Israel. FAU - Golan, Matan AU - Golan M AD - Department of Poultry and Aquaculture, Institute of Animal Sciences, Agricultural Research Organization, Volcani Center, Rishon Letziyon 7505101, Israel. FAU - Gothilf, Yoav AU - Gothilf Y AD - Department of Neurobiology, George S. Wise Faculty of Life Sciences and Sagol School of Neurosciences, University of Tel Aviv, Tel Aviv 69978, Israel. Electronic address: yoavgothilf@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200527 PL - United States TA - Gen Comp Endocrinol JT - General and comparative endocrinology JID - 0370735 RN - 0 (Gonadotropins) RN - 0 (Kisspeptins) RN - 0 (RNA, Messenger) RN - 0 (Zebrafish Proteins) SB - IM MH - Animals MH - Base Sequence MH - Brain/metabolism MH - Female MH - Gene Expression Regulation MH - Gene Knockout Techniques MH - Gonadotropins/genetics/metabolism MH - Kisspeptins/*metabolism MH - Male MH - Mutation/genetics MH - RNA, Messenger/genetics/metabolism MH - Reproduction/genetics MH - Zebrafish/*metabolism MH - Zebrafish Proteins/genetics/*metabolism OTO - NOTNLM OT - Compensatory mechanism OT - Kisspeptin OT - Knockout OT - Reproduction OT - Tachykinin OT - Zebrafish EDAT- 2020/05/30 06:00 MHDA- 2020/12/19 06:00 CRDT- 2020/05/30 06:00 PHST- 2020/03/08 00:00 [received] PHST- 2020/05/19 00:00 [revised] PHST- 2020/05/22 00:00 [accepted] PHST- 2020/05/30 06:00 [pubmed] PHST- 2020/12/19 06:00 [medline] PHST- 2020/05/30 06:00 [entrez] AID - S0016-6480(20)30276-8 [pii] AID - 10.1016/j.ygcen.2020.113523 [doi] PST - ppublish SO - Gen Comp Endocrinol. 2020 Sep 1;295:113523. doi: 10.1016/j.ygcen.2020.113523. Epub 2020 May 27.