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Pharmacological and Genetic Disruption of C-Type Natriuretic Peptide (nppcl) Expression in Zebrafish (Danio rerio) Causes Stunted Growth during Development

Lessey, Andrew J.; Mirczuk, Samantha M.; Chand, Annisa N.; Kurrasch, Deborah M.; Korbonits, Márta; Niessen, Stijn J. M.; McArdle, Craig A.; McGonnell, Imelda M.; Fowkes, Robert C.


Andrew J. Lessey

Samantha M. Mirczuk

Annisa N. Chand

Deborah M. Kurrasch

Márta Korbonits

Stijn J. M. Niessen

Craig A. McArdle

Imelda M. McGonnell

Robert C. Fowkes


Imelda McGonnell


Human patients with mutations within NPPC or NPR2 genes (encoding C-type natriuretic peptide (CNP) and guanylyl cyclase-B (GC-B), respectively) display clinical signs associated with skeletal abnormalities, such as overgrowth or short stature. Mice with induced models of Nppc or Npr2 deletion display profound achondroplasia, dwarfism and early death. Recent pharmacological therapies to treat short stature are utilizing long-acting CNP analogues, but the effects of manipulating CNP expression during development remain unknown. Here, we use Danio rerio (zebrafish) as a model for vertebrate development, employing both pharmacological and reverse genetics approaches to alter expression of genes encoding CNP in zebrafish. Four orthologues of CNP were identified in zebrafish, and spatiotemporal expression profiling confirmed their presence during development. Bioinformatic analyses suggested that nppcl is the most likely the orthologue of mammalian CNP. Exogenous CNP treatment of developing zebrafish embryos resulted in impaired growth characteristics, such as body length, head width and eye diameter. This reduced growth was potentially caused by increased apoptosis following CNP treatment. Expression of endogenous nppcl was downregulated in these CNP-treated embryos, suggesting that negative feedback of the CNP system might influence growth during development. CRISPR knock-down of endogenous nppcl in developing zebrafish embryos also resulted in impaired growth characteristics. Collectively, these data suggest that CNP in zebrafish is crucial for normal embryonic development, specifically with regard to growth.
Keywords: zebrafish; natriuretic peptides; growth


Lessey, A. J., Mirczuk, S. M., Chand, A. N., Kurrasch, D. M., Korbonits, M., Niessen, S. J. M., …Fowkes, R. C. (2023). Pharmacological and Genetic Disruption of C-Type Natriuretic Peptide (nppcl) Expression in Zebrafish (Danio rerio) Causes Stunted Growth during Development. International Journal of Molecular Sciences, 24(16), 12921.

Journal Article Type Article
Acceptance Date Aug 14, 2023
Online Publication Date Aug 18, 2023
Publication Date Aug 18, 2023
Deposit Date Aug 22, 2023
Publicly Available Date Aug 23, 2023
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 24
Issue 16
Pages 12921
Keywords zebrafish; natriuretic peptides; growth
Publisher URL


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