We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Zebrafish nampt-a mutants are viable despite perturbed primitive hematopoiesis.
- Authors
Pomreinke, Autumn Penecilla; Müller, Patrick
- Abstract
Background: Nicotinamide phosphoribosyltransferase (Nampt) is required for recycling NAD+ in numerous cellular contexts. Morpholino-based knockdown of zebrafish nampt-a has been shown to cause abnormal development and defective hematopoiesis concomitant with decreased NAD+ levels. However, surprisingly, nampt-a mutant zebrafish were recently found to be viable, suggesting a discrepancy between the phenotypes in knockdown and knockout conditions. Here, we address this discrepancy by directly comparing loss-of-function approaches that result in identical defective transcripts in morphants and mutants. Results: Using CRISPR/Cas9-mediated mutagenesis, we generated nampt-a mutant lines that carry the same mis-spliced mRNA as nampt-a morphants. Despite reduced NAD+ levels and perturbed expression of specific blood markers, nampt-a mutants did not display obvious developmental defects and were found to be viable. In contrast, injection of nampt-a morpholinos into wild-type or mutant nampt-a embryos caused aberrant phenotypes. Moreover, nampt-a morpholinos caused additional reduction of blood-related markers in nampt-a mutants, suggesting that the defects observed in nampt-a morphants can be partially attributed to off-target effects of the morpholinos. Conclusions: Our findings show that zebrafish nampt-a mutants are viable despite reduced NAD+ levels and a perturbed hematopoietic gene expression program, indicating strong robustness of primitive hematopoiesis during early embryogenesis.
- Subjects
BRACHYDANIO; GENE expression; HEMATOPOIESIS; PHENOTYPES; CRISPRS; NICOTINAMIDE
- Publication
Hereditas, 2024, Vol 161, Issue 1, p1
- ISSN
0018-0661
- Publication type
Article
- DOI
10.1186/s41065-024-00318-y