Dilated rough endoplasmic reticulum and premature death in melanocytes cultured from the vitiligo mouse.
It has been proposed that the selective melanocyte destruction in hair bulbs of the murine model for vitiligo (VIT) is instigated by either the local cutaneous environment or an innate melanocyte defect. To address this problem, the authors have isolated the melanocyte population from environmental influences by using cell culture technology and have observed reduced proliferation, specific cytologic abnormalities, and premature cell death in cultures of pure VIT melanocytes established from neonatal skin. Cultured VIT melanocytes manifest abnormal compartmentalization of melanosomes and some aberrant dihydroxyphenylalanine-positive structures. The most prominent abnormality observed in cultured VIT melanocytes when compared with the control C57BL/6J cells is a development in dilation of the rough endoplasmic reticulum (RER) that morphologically resembles the in vivo condition. Dilation of the RER can be exaggerated in VIT or induced in C57BL/6J melanocytes by the addition of Brefeldin A to cultures. Conversely the dilated RER cisternae characteristic of the VIT melanocyte can be reversed by inhibition of protein synthesis with cyclobeximide. Melanocyte cultures developed from heterozygote neonates, resulting from cross-breedings between the VIT and the C57BL/6J lines, also demonstrated extensive RER dilation along with only slightly reduced proliferation. The results in this report verify that the murine vitiligo melanocyte expresses an innate defect that affects the structure and presumably the function of the rough endoplasmic reticulum.
Boissy
R E
RE
Department of Dermatology, University of Cincinnati College of Medicine, OH 45267-0592.
Beato
K E
KE
Nordlund
J J
JJ
D000818:Animals; D020126:Brefeldin A; D002470:Cell Survival; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure*; D008544:Melanocytes / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D013997:Time Factors; D014820:Vitiligo / Q000235:genetics / Q000473:pathology*
D003517:Cyclopentanes; D020126:Brefeldin A; D003513:Cycloheximide