Development of the Swimbladder Surfactant System and Biogenesis of Lysosome-Related Organelles Is Regulated by BLOS1 in Zebrafish

• Published in: Genetics (Austin) Vol. 208; no. 3; pp. 1131 - 1146
• Main Authors: Chen, Tianbing, Song, Guili, Yang, Huihui, Mao, Lin, Cui, Zongbin, Huang, Kaiyao
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01.03.2018
• Subjects: Air Sacs - metabolism; Air Sacs - ultrastructure; Albinism; Animals; Animals, Genetically Modified; Biosynthesis; Danio rerio; Defects; Evolution; Eye Proteins - chemistry; Eye Proteins - genetics; Eye Proteins - metabolism; Gene expression; Gene Expression Regulation; Genes; Genetics; Hereditary diseases; Hermanski-Pudlak Syndrome - genetics; Hermanski-Pudlak Syndrome - metabolism; Hermansky-Pudlak syndrome; Homeostasis; Investigations; Lethality; Lungs; Lysosomes - metabolism; Lysosomes - ultrastructure; Mammals; Melanin; Mutation; Organelles; Organelles - metabolism; Organelles - ultrastructure; Pathogenesis; Phenotype; Protein Subunits; Proteins; Surface-Active Agents - metabolism; Surfactants; Zebrafish; Zebrafish - physiology; lysosome-related organelles; surfactant system; swimbladder; Hermansky-Pudlak syndrome
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.117.300621

Hermansky-Pudlak syndrome (HPS) is a human autosomal recessive disorder that is characterized by oculocutaneous albinism and a deficiency of the platelet storage pool resulting from defective biogenesis of lysosome-related organelles (LROs). To date, 10 HPS genes have been identified, three of which belong to the octamer complex BLOC-1 (biogenesis of lysosome-related organelles complex 1). One subunit of the BLOC-1 complex, BLOS1, also participates in the BLOC-1-related complex (BORC). Due to lethality at the early embryo stage in BLOS1 knockout mice, the function of BLOS1 in the above two complexes and whether it has a novel function are unclear. Here, we generated three zebrafish mutant lines with a BLOC-1 deficiency, in which melanin and silver pigment formation was attenuated as a result of mutation of , , and , suggesting that they function in the same complex. In addition, mutations of and caused an accumulation of clusters of lysosomal vesicles at the posterior part of the tectum, representing a BORC-specific function in zebrafish. Moreover, is highly expressed in the swimbladder during postembryonic stages and is required for positively regulating the expression of the genes, which is known to govern surfactant production and lung development in mammals. Our study identified BLOS1 as a crucial regulator of the surfactant system. Thus, the zebrafish swimbladder might be an easy system to screen and study genetic modifiers that control surfactant production and homeostasis.