The kiss/kissr systems are dispensable for zebrafish reproduction: evidence from gene knockout studies

Endocrinology. 2015 Feb;156(2):589-99. doi: 10.1210/en.2014-1204. Epub 2014 Nov 18.


The kiss1/gpr54 signaling system is considered to be a critical regulator of reproduction in most vertebrates. However, this presumption has not been tested vigorously in nonmammalian vertebrates. Distinct from mammals, multiple kiss1/gpr54 paralogous genes (kiss/kissr) have been identified in nonmammalian vertebrates, raising the possibility of functional redundancy among these genes. In this study, we have systematically generated the zebrafish kiss1(-/-), kiss2(-/-), and kiss1(-/-);kiss2(-/-) mutant lines as well as the kissr1(-/-), kissr2(-/-), and kissr1(-/-);kissr2(-/-) mutant lines using transcription activator-like effector nucleases. We have demonstrated that spermatogenesis and folliculogenesis as well as reproductive capability are not impaired in all of these 6 mutant lines. Collectively, our results indicate that kiss/kissr signaling is not absolutely required for zebrafish reproduction, suggesting that the kiss/kissr systems play nonessential roles for reproduction in certain nonmammalian vertebrates. These findings also demonstrated that fish and mammals have evolved different strategies for neuroendocrine control of reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Follicle Stimulating Hormone, beta Subunit / metabolism
  • Gene Knockout Techniques
  • Gonadotropin-Releasing Hormone / metabolism
  • Kisspeptins / genetics
  • Kisspeptins / metabolism*
  • Luteinizing Hormone, beta Subunit / metabolism
  • Male
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Kisspeptin-1
  • Reproduction*
  • Sexual Maturation
  • Zebrafish / physiology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Follicle Stimulating Hormone, beta Subunit
  • Kiss1 protein, zebrafish
  • Kisspeptins
  • Luteinizing Hormone, beta Subunit
  • Receptors, G-Protein-Coupled
  • Receptors, Kisspeptin-1
  • Zebrafish Proteins
  • kiss1ra protein, zebrafish
  • Gonadotropin-Releasing Hormone