Impaired Motor Function in a Zebrafish Stathmin-2 Knockout Model

Stathmin-2 (STMN2) is a microtubule-associated protein that plays a role in the stability of microtubules in axons of the nervous system of animals. In this study, we generated a novel zebrafish STMN2 knockout (KO) model. STMN2 is represented by two genes in the zebrafish genome: stmn2a and stmn2b. Using the CRISPR/Cas9 mutagenic system, we selected founder fish lines harboring frameshift mutations in both genes and bred these together to generate a double stmn2a and stmn2b KO model. Using these models, we observed increased developmental lethality in our double stmn2a and stmn2b KO model and impaired motor function at embryonic stages of development. Examination of the neuromuscular junction (NMJ) revealed a slight increase in the number of orphaned NMJs in trunk musculature as well as a reduction in the amplitude of miniature endplate currents in our double stmn2a and stmn2b KO model. In a final series of experiments, we show impaired ventral root axon regrowth following transection in double stmn2a and stmn2b KO zebrafish. Our findings suggest that while not essential for motor function development, loss of stmn2a and stmn2b expression results in a minor motor phenotype and impairs the ability to regenerate motor axons following injury.