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.

Kisspeptin（KISS）是一种神经肽，在下丘脑-垂体-性腺轴的调节中起着核心作用，对于哺乳动物的性成熟和生育至关重要。与仅拥有一个KISS基因的哺乳动物不同，在斑马鱼和其他非哺乳动物脊椎动物中已经鉴定出两个同源的基因kiss1和kiss2。先前的研究表明，Kiss2（而非Kiss1）是两者中与繁殖相关的形式。为了更好地理解这些同工型在生殖中的作用，应用了功能丧失方法。两种遗传操作技术-产生规则间隔的短回文重复序列（CRISPR）和转录激活因子样效应核酸酶（TALEN）-用来产生kiss1和kiss2敲除（KO）斑马鱼线。对这些KO系的检查表明，生殖能力未受到损害，这证实了较早的观察结果。进一步分析发现，KO的kiss2引起的表达水平的显著上升KISS1，kiss2r和tac3a，而KO KISS1对任何检测基因的表达没有影响。原位杂交分析表明，kiss1 mRNA仅在野生型大脑的唇形物中表达，而在kiss2 KO鱼中，kiss1在腹侧端脑，上皮髓核的腹侧部分以及背侧和腹侧下丘脑中也发现了表达mRNA的细胞。有趣的是，已知这些区域表达kiss2r，腹侧下丘脑通常表达kiss2。这些结果表明，在kiss2 KO鱼中发生了涉及异位kiss1表达的补偿机制，这可能替代了Kiss2的活性。