{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:55:49Z","timestamp":1782453349385,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT093257MA"],"award-info":[{"award-number":["WT093257MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["BB\/L002795\/1"],"award-info":[{"award-number":["BB\/L002795\/1"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Society for Endocrinology","award":["WT093257MA"],"award-info":[{"award-number":["WT093257MA"]}]},{"name":"Society for Endocrinology","award":["BB\/L002795\/1"],"award-info":[{"award-number":["BB\/L002795\/1"]}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["WT093257MA"],"award-info":[{"award-number":["WT093257MA"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/L002795\/1"],"award-info":[{"award-number":["BB\/L002795\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms241612921","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T10:14:38Z","timestamp":1692353678000},"page":"12921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacological and Genetic Disruption of C-Type Natriuretic Peptide (nppcl) Expression in Zebrafish (Danio rerio) Causes Stunted Growth during Development"],"prefix":"10.3390","volume":"24","author":[{"given":"Andrew J.","family":"Lessey","sequence":"first","affiliation":[{"name":"Endocrine Signalling Group, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"},{"name":"Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Mirczuk","sequence":"additional","affiliation":[{"name":"Endocrine Signalling Group, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"},{"name":"Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annisa N.","family":"Chand","sequence":"additional","affiliation":[{"name":"Endocrine Signalling Group, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"},{"name":"Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M.","family":"Kurrasch","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Calgary, Calgary, AB T2N 4N2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-9432","authenticated-orcid":false,"given":"M\u00e1rta","family":"Korbonits","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn J. M.","family":"Niessen","sequence":"additional","affiliation":[{"name":"Clinical Sciences & Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK"},{"name":"Veterinary Specialist Consultations, Loosdrechtseweg 56, 1215 JX Hilversum, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"McArdle","sequence":"additional","affiliation":[{"name":"Department of Translational Science, Bristol Medical School, University of Bristol, Whitson Street, Bristol BS1 3NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9800-7248","authenticated-orcid":false,"given":"Imelda M.","family":"McGonnell","sequence":"additional","affiliation":[{"name":"Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2222-2056","authenticated-orcid":false,"given":"Robert C.","family":"Fowkes","sequence":"additional","affiliation":[{"name":"Endocrine Signalling Group, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"},{"name":"Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK"},{"name":"Endocrine Signaling Group, Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, Wilson Road, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1210\/er.2005-0014","article-title":"Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions","volume":"27","author":"Potter","year":"2006","journal-title":"Endocr. 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