Zebrafish model for diseases caused by ER stress

Mutations in human SEC63 cause polycystic liver disease (PCLD). Because Sec63 is a component of the endoplasmic reticulum (ER) translocon machinery, it has been proposed that SEC63 mutations cause PCLD by triggering ER stress, activation of which is also linked to myelin disorders. Monk et al. now describe a zebrafish mutant that was isolated in a screen for mutations affecting the development of myelinated axons. The mutant carries sec63^st67, a missense mutation in the zebrafish ortholog of Sec63. The researchers report that liver cells and nervous system cells in sec63^st67 mutants show a swollen and fragmented ER, and express molecular markers of ER stress. sec63^st67 mutants could therefore serve as a model for studying the role of ER stress in PCLD and in myelin disorders. Page 135