Knockout of the fcsk gene in zebrafish causes neurodevelopmental defects

Congenital disorders of glycosylation (CDG) are a cluster of monogenic disorders resulting from defects in glycosylation. FCSK encodes fucokinase, an enzyme that catalyzes the phosphorylation of L-fucose to generate fucose-1-phosphate, an important step in fucosylation. Mutations in FCSK lead to CDG with an autosomal recessive inheritance pattern, primarily manifesting as developmental delay, hypotonia, and brain abnormalities. However, no fcsk mutant animal models have yet been established. This study constructed the first fcsk knockout ( fcsk ^-/-) zebrafish model using CRISPR/Cas9 technology. Notably, fcsk ^-/- zebrafish exhibited impaired growth, characterized by delayed epiboly and DNA accumulation during early embryonic development, as well as brain atrophy in adulthood.