|ZFIN ID: ZDB-PUB-170428-2|
Novel Degenerative and Developmental Defects in a Zebrafish Model of Mucolipidosis Type IV
Li, H., Pei, W., Vergarajauregui, S., Zerfas, P.M., Raben, N., Burgess, S.M., Puertollano, R.
|Source:||Human molecular genetics 26(14): 2701-2718 (Journal)|
|Registered Authors:||Burgess, Shawn, Pei, Wuhong, Puertollano, Rosa, Raben, Nina|
|Keywords:||immunohistochemistry, embryo, genes, auditory hair cell, zebrafish, pathology, mucolipidosis iv, autophagosomes|
|PubMed:||28449103 Full text @ Hum. Mol. Genet.|
Li, H., Pei, W., Vergarajauregui, S., Zerfas, P.M., Raben, N., Burgess, S.M., Puertollano, R. (2017) Novel Degenerative and Developmental Defects in a Zebrafish Model of Mucolipidosis Type IV. Human molecular genetics. 26(14):2701-2718.
ABSTRACTMucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family. In this study we used genome editing to knockout the two mcoln1 genes present in Danio rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis. Importantly, our model revealed novel insights into the origins and progression of the MLIV pathology, including the contribution of autophagosome accumulation to muscle dystrophy and the role of mcoln1 in embryonic development, hair cell viability and cellular maintenance. The generation of a MLIV model in zebrafish is particularly relevant given the suitability of this organism for large-scale in vivo drug screening, thus providing unprecedented opportunities for therapeutic discovery.