Pigmentation is regulated to a large extent by the levels of tyrosinase activity as indicated by tyrosinase measurements in vitro. Surprisingly, therefore, approximately half of the human population of albinos is tyrosinase-positive (Witkop et al, 1983), an indication of the existence of additional regulatory factors that are operative in normal pigmentation but not in tyrosinase-positive albinism. In mice at least 50 genetic loci outside the tyrosinase-or c-locus are known to affect pigmentation (Silver, 1979), one of these being the brown or b-locus, but little is known about the molecular basis for any of these genetic coat color variations.

We have carried out immunoprecipitation studies using anti-tyrosinase antibodies. TMH-1 and anti-PEP1 antibodies to the brown-locus protein (Tomita et al, 1985; Jimenez et al, 1988), demonstrating that two melanocyte-specific glycoproteins have catalase activity. One of these, which we call catalase-Br, segregates with the murine brown coat color locus, and the other, which we call P-catalase, does not. In human melanocytes the abundance of immunoprecipitated catalase-Br correlates with the amount of melanin more so than does tyrosinase. Because H₂0₂ may be a byproduct of tyrosinase activity and is known to destroy melanin precursors, we conclude that pigmentation is controlled not only by tyrosinase, but also by enzymes that decompose H₂0₂. Thus, mutations that decrease the activities of these two catalases may be the reason for the absence of eumelanin in red hair and tyrosinase-positive albinos.

References
Jimenez M et al: J Biol Chem 264:3397-3403.
Silver WK: The Coat Colors of Mice, Springer-Verlag, NY, 1979.
Tomita Y et al : J Invest Dermatol 85:426-430.
Witkop Jr CJ et al : In: Metabolic basis of inherited disease (Stanbury JB et al. eds), McGraw-Hill, NY, 301-346.


Ruth Halaban and Gisela Moellman
Dept of Dermatology
Yale University School of Medicine
500 LCI, PO Box 3333
New Haven, Connecticut 065:0-8059