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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.

Current pet diabetes mellitus (DM) treatment necessitates the active daily involvement of owners and can be costly. The current study aimed to investigate the owner population which opts for euthanasia instead of DM treatment. A survey was designed using multiple feedback steps and made available online to veterinarians world-wide. A total of 1192 veterinarians completed the survey and suggested a median one in 10 diabetic pets are euthanased at diagnosis; a further median one in 10 within one year because of lack of success or compliance. Perceived most important motivating factors included "presence concurrent disease" (45% respondents); "costs" (44%); "animal age" (37%); "problems obtaining adequate control" (35%); "pet welfare" (35%); and "impact owner's lifestyle" (32%). Cats in Canadian (odds ratio (OR) 2.7), Australian (OR 2.3), rural (OR 1.6) and mixed (OR 1.7) practices were more likely to be euthanased because of DM diagnosis, while cats presented to referral/university were less likely to be euthanased (OR 0.6). Dogs were more likely to be euthanased because of DM in Canadian (OR 1.8), rural (OR 1.8) and mixed (OR 1.6) practices. The survey results suggest that benefit exists in improved DM education with emphasis on offering a choice of treatment styles ranging from intense and expensive to hands-off and cheap., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.