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Molecular and Cellular Biology, April 2004, p. 3396-3403, Vol. 24, No. 8
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.8.3396-3403.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Melanocytes and Pigmentation Are Affected in Dopachrome Tautomerase Knockout Mice

Laurence Guyonneau,1,{dagger} Fabien Murisier,1,{dagger} Anita Rossier,1,{dagger} Alexandre Moulin,2 and Friedrich Beermann1*

Molecular Oncology, Swiss Institute for Experimental Cancer Research, National Center of Competence in Research, 1066 Epalinges,1 Institute of Pathology, University of Lausanne, 1005 Lausanne, Switzerland2

Received 27 October 2003/ Returned for modification 7 December 2003/ Accepted 31 January 2004

The tyrosinase family comprises three members, tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and dopachrome tautomerase (Dct). Null mutations and deletions at the Tyr and Tyrp1 loci are known and phenotypically affect coat color due to the absence of enzyme or intracellular mislocalization. At the Dct locus, three mutations are known that lead to pigmentation phenotype. However, these mutations are not null mutations, and we therefore set out to generate a null allele at the Dct gene locus by removing exon 1 of the mouse Dct gene. Mice deficient in Dct [Dcttm1(Cre)Bee] lack Dct mRNA and dopachrome tautomerase protein. They are viable and do not show any abnormalities in Dct-expressing sites such as skin, retinal pigment epithelium, or brain. However, the mice show a diluted coat color phenotype, which is due to reduced melanin content in hair. Primary melanocytes from Dct knockout mice are viable in culture and show a normal distribution of tyrosinase and tyrosinase-related protein 1. In comparison to the knockout, the slaty mutation (Dctslt/Dctslt) has less melanin and affects growth of primary melanocytes severely. In summary, we have generated a knockout of the Dct gene in mice with effects restricted to pigment production and coat color.

* Corresponding author. Mailing address: ISREC, Chemin des Boveresses 155, 1066 Epalinges, Switzerland. Phone: 41-21 692 5914. Fax: 41-21-652 6933. E-mail: Friedrich.Beermann{at}isrec.unil.ch.

{dagger} L.G., F.M., and A.R. contributed equally to this work.

Molecular and Cellular Biology, April 2004, p. 3396-3403, Vol. 24, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.8.3396-3403.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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