TY - JOUR
T1 - Ectopic over expression of kiss1 may compensate for the loss of kiss2
AU - Etzion, Talya
AU - Zmora, Nilli
AU - Zohar, Yonatan
AU - Levavi-Sivan, Berta
AU - Golan, Matan
AU - Gothilf, Yoav
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
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.
KW - Compensatory mechanism
KW - Kisspeptin
KW - Knockout
KW - Reproduction
KW - Tachykinin
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85086565203&partnerID=8YFLogxK
U2 - 10.1016/j.ygcen.2020.113523
DO - 10.1016/j.ygcen.2020.113523
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C2 - 32470472
AN - SCOPUS:85086565203
SN - 0016-6480
VL - 295
JO - General and Comparative Endocrinology
JF - General and Comparative Endocrinology
M1 - 113523
ER -