title: The Ap3b1 gene regulates the ocular melanosome biogenesis and tyrosinase distribution differently from the Hps1 gene.
abstract: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. The pearl (pe) mouse, a mouse model for the human HPS-2, bears a mutation in Ap3b1 gene. Here we investigated the pigmentation in eyes of pearl (pe) mice, and compared it with our previously published data in pale ear (ep) mice. We revealed that the hypopigmentation in eyes of pearl mice was more severe than pale ear mice, especially in the neural crest-derived tissues. However, the total tyrosinase activity in eyes of pearl mice was stronger than pale ear mice, suggesting that the degradation of aberrantly transported tyrosinase in eyes of pearl mice was weaker than that of pale ear mice. Furthermore, the pigmentation in eyes of mice doubly heterozygous for Hps1 and Ap3b1 genes was similar to the wild-type, while the hypopigmentation in iris of double mutant mice was more severe than either single mutant. Besides, we found several previously reported characters in pale ear mice, including macromelanosomes in the neural crest-derived melanocytes and increased accumulation of lipofuscin in the RPE, were absent in pearl mice. Our study indicates that Ap3b1 gene play distinct roles in melanin production and tyrosinase distribution compared with Hps1 gene.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, 250100, PR China; Basic Medical College, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, PR China. Electronic address: renwei9128@126.com.
authors.forename: Renwei
authors.initials: R
authors.lastname: Jing
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, 250100, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Dong
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, 250100, PR China; Central Research Laboratory, The Second Hospital of Shandong University, Jinan, 250100, PR China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, 250100, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, 250100, PR China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, 250100, PR China. Electronic address: drfeng@sdu.edu.cn.
authors.forename: Lijun
authors.initials: L
authors.lastname: Feng
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000235:genetics*; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics*; D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism*; D015153:Blotting, Western; D004195:Disease Models, Animal; D005127:Eye Color; D005786:Gene Expression Regulation / Q000502:physiology*; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017496:Hypopigmentation / Q000378:metabolism*; D008062:Lipofuscin / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D012880:Skin Pigmentation
chemical_list: D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; C418506:Ap3b1 protein, mouse; C491131:Hps1 protein, mouse; D008062:Lipofuscin; D008543:Melanins; D008565:Membrane Proteins; D014442:Monophenol Monooxygenase
keywords: development; double mutant; embryonic origin; hypopigmentation; lipofuscin; tyrosinase