Disease modifying function of MAP2K5 in the zebrafish model of ALS. Knockdown of MAP2K5 rescued mutant OPTN- and ANG-induced motor axonopathy. (A,B) Expression of EGFP-tagged MAP2K5 protein in embryos injected with scrambled MO (A) and map2k5 MO (B) along with the cmv:map2k5-egfp construct. (C–N) Lateral views of the spinal cords of Tg(olig2:dsred2) embryos, with anterior to the left and dorsal to the top. Motor axons and NMJs were detected from DsRed fluorescent protein expression. (C–H) The spinal cord of Tg(olig2:dsred2) embryos was injected with scrambled MO and GFP (C), OPTN E50K (D) or OPTN E478G (E) mRNA, or injected with map2k5 MO and GFP (F), OPTN E50K (G), or OPTN E478G (H) mRNA. (I–N) The spinal cord of Tg(olig2:dsred2) embryos was injected with scrambled MO and ANG K17I (I), ANG K40I (J), or ANG P112L (K) mRNA, or injected with map2k5 MO and ANG K17I (L), ANG K40I (M), or ANG P112L (N) mRNA. (O) Statistical analysis of C–N. Data were obtained from 10 control and 10 mRNA-injected embryos. (*) P < 0.05 between the indicated groups; mean ± SD.
