Postnatal ocular expression of tyrosinase and related proteins: disruption by the pink-eyed unstable (p(un)) mutation.
Ocular pigmentation in the mouse occurs primarily postnatally as a result of the melanization of neural crest-derived melanocytes. Using immunologic and biochemical techniques, we demonstrate that in normal mice the expression of tyrosinase and the related proteins TRP-1 and TRP-2, rises during the first week of life, remains elevated for a week, and then steadily declines to low levels by adulthood. Sucrose gradient density centrifugation demonstrates that tyrosinase, TRP-1 and TRP-2 are present in high molecular weight forms in the eyes of wild-type mice. The normal time course is disrupted in mice carrying the pink-eyed unstable (p(un)) mutation at the P-locus, a model for tyrosinase-positive albinism in man. Tyrosinase and TRP-2 are present at wild-type levels in the eyes of p(un)/p(un) mice at birth, but, rather than rising, their levels rapidly decline over the first week of life. TRP-1 is almost undetectable, even at birth. High molecular weight complexes could not be detected in eyes of p(un)/p(un) mice. Our results suggest that postnatal ocular melanogenesis in the mouse presents an attractive model for the study of the orderly expression and action of the proteins involved in eumelanin synthesis, and that the p(un) mutation disrupts this temporally controlled process.
Chiu
E
E
Ronald O. Perelman Department of Dermatology, New York University School of Medicine, NY.
Lamoreux
M L
ML
Orlow
S J
SJ
D000417:Albinism / Q000378:metabolism*; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005123:Eye / Q000201:enzymology*; D005127:Eye Color / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009154:Mutation; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D014442:Monophenol Monooxygenase