Elovl2 but not Elovl5 is essential for the biosynthesis of docosahexaenoic acid (DHA) in zebrafish: insight from a comparative gene knockout study

Teleost fish can synthesize one of the major omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), docosahexaenoic acid (DHA, 22:6n-3), from dietary α-linolenic acid (ALA; 18:3n-3), via elongase of very long chain fatty acid (Elovl) and fatty acid desaturase (Fads). However, it remains unclear which elongase is responsible for the endogenous synthesis of DHA. Here in this study, the knockout models of the two major elongases, Elovl2 and Elovl5, were generated by CRISPR/Cas9 approach in zebrafish and comparatively analyzed. The homozygous mutants were validated by Sanger sequencing, mutation-mediated PCR and whole-mount in situ hybridization analysis of the endogenous target genes. Compared with wildtype (WT) counterparts, the content of DHA was significantly reduced by 67.1% (p