- Title
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A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects
- Authors
- Zhang, J., Lachance, V., Schaffner, A., Li, X., Fedick, A., Kaye, L.E., Liao, J., Rosenfeld, J., Yachelevich, N., Chu, M.L., Mitchell, W.G., Boles, R.G., Moran, E., Tokita, M., Gorman, E., Bagley, K., Zhang, W., Xia, F., Leduc, M., Yang, Y., Eng, C., Wong, L.J., Schiffmann, R., Diaz, G.A., Kornreich, R., Thummel, R., Wasserstein, M., Yue, Z., Edelmann, L.
- Source
- Full text @ PLoS Genet.
Significant cell death is observed in the CNS of zebrafish vps11(plt) mutants.TUNEL assay was performed on cryosectioned CNS tissue from vps11(plt) mutants and wild-type siblings at 3, 5, and 7 days post-fertilization (dpf). (A-C) Minimal apoptotic TUNEL+ cells were observed in the hindbrain of vps11(plt) mutants at 3, 5, and 7 dpf, respectively. (D-E) Tissue section of the midbrain of a wild-type control animal at 7 dpf showing minimal cell death (panel E, arrow). (F-G) Tissue section of the midbrain of a vps11(plt) mutant at 7 dpf showing extensive cell death. (H) Quantification of the average number of TUNEL+ cells observed in the hindbrain in vps11(plt) mutants and wild-type siblings at 3, 5, and 7 dpf. No significant differences were observed. (I) Quantification of the average number of TUNEL+ cells observed in the midbrain in vps11(plt) mutants and wild-type siblings at 3, 5, and 7 dpf. Asterisk indicates significantly different from control. PHENOTYPE:
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Progressive loss of myelination in zebrafish vps11(plt) mutants.Cryosectioned CNS tissue from vps11(plt) mutants and wild-type siblings were immunolabeled with Mbp (myelin; green) and HuCD (neurons; red) at 3 and 5 dpf. (A-A′′) Mbp immunolocalization to Mauthner axons in the hindbrain of wild-type animals at 5 dpf (arrows). (B-B′′) Mbp immunolocalization to Mauthner axons in the hindbrain of vps11(plt) mutants at 5 dpf (arrows). (C-C′′) Mbp immunolocalization in the hindbrain of wild-type animals at 7 dpf. (D-D′′) Significant reduction in Mbp immunolocalization in the hindbrain of vps11(plt) mutants at 7 dpf. |
Significant cell death in the CNS of zebrafish vps11(plt) mutants.Activated Caspase-3 was performed on cryosectioned CNS tissue from vps11(plt) mutants and wild-type siblings at 7 days post-fertilization (dpf). A) Wild-type hindbrain shows minimal apoptotic cells (arrow). B) Many apoptotic cells were observed in the vps11(plt) mutants. C) Quantification of the average number of Caspase-3+ cells observed in the hindbrain of vps11(plt) mutants and wild-type siblings at 7 dpf. Asterisk indicates significantly different from control. PHENOTYPE:
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