Hirobe Tomohisa, Ishizuka Kenji, Ogawa Shigeru, Abe Hiroyuki
Radiation Effect Mechanism Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Zoolog Sci. 2008 Nov;25(11):1057-65. doi: 10.2108/zsj.25.1057.
Abstract The mouse pink-eyed dilution (p) locus is known to control the melanin content in melanocytes. However, it was not known whether the p gene is involved in regulating the proliferation and differentation of melanocytes during development, especially the biogenesis of melanosomes and other organelles. Epidermal cell suspensions of neonatal dorsal skin derived from mice wild type for the p locus (black, C57BL/10JHir-P/P) and their congenic mutant phenotype (pink-eyed dilution, C57BL/10JHir-p/p) were cultured in serum-free melanocyte-proliferation medium (MDMD). The supplement of additional L-tyrosine (Tyr) into the MDMD stimulated the differentiation of p/p melanoblasts into melanocytes. Electron microscopy revealed that in p/p melanoblasts and melanocytes treated with L-Tyr, the number of stage II and III melanosomes dramatically increased. Moreover, p/p melanoblasts possessed smaller but more numerous mitochondria than P/P melanocytes. The treatment of p/p melanoblasts and melanocytes with L-Tyr decreased the number of mitochondria. The supplement of 2, 4-dinitrophenol (DNP), an inhibitor of mitochondrial function, into the MDMD stimulated both the proliferation and differentiation of p/p melanoblasts. Simultaneous treatment of DNP and L-Tyr dramatically stimulated the differetiation of p/p melanocytes. These results suggest that L-Tyr and some unknown factors related to mitochondrial function may influence the differentiation of melanoblasts in the epidermis of p/p mice.
摘要 已知小鼠粉红眼稀释(p)基因座控制黑素细胞中的黑色素含量。然而,尚不清楚p基因在发育过程中是否参与调节黑素细胞的增殖和分化,特别是黑素小体和其他细胞器的生物发生。将来自p基因座野生型小鼠(黑色,C57BL/10JHir-P/P)及其同基因突变异型(粉红眼稀释,C57BL/10JHir-p/p)的新生背部皮肤的表皮细胞悬液在无血清黑素细胞增殖培养基(MDMD)中培养。向MDMD中添加额外的L-酪氨酸(Tyr)刺激了p/p黑素母细胞向黑素细胞的分化。电子显微镜显示,在用L-Tyr处理的p/p黑素母细胞和黑素细胞中,II期和III期黑素小体的数量显著增加。此外,p/p黑素母细胞比P/P黑素细胞拥有更小但更多的线粒体。用L-Tyr处理p/p黑素母细胞和黑素细胞可减少线粒体数量。向MDMD中添加线粒体功能抑制剂2,4-二硝基苯酚(DNP)刺激了p/p黑素母细胞的增殖和分化。同时用DNP和L-Tyr处理显著刺激了p/p黑素细胞的分化。这些结果表明,L-Tyr和一些与线粒体功能相关的未知因素可能影响p/p小鼠表皮中黑素母细胞的分化。