Nature Genetics 33, 145 - 153 (2003)
Published online: 27 January 2003; | doi:10.1038/ng1087
Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6Qing Zhang1, 9, Baohui Zhao1, 9, Wei Li1, 9, Naoki Oiso2, 9, Edward K. Novak1, Michael E. Rusiniak1, Rashi Gautam1, Sreenivasulu Chintala1, Edward P. O'Brien1, Yuke Zhang1, Bruce A. Roe3, Rosemary W. Elliott1, Eva M. Eicher4, Ping Liang5, Christian Kratz6, Eric Legius7, Richard A. Spritz2, T. Norene O'Sullivan8, Neal G. Copeland8, Nancy A. Jenkins8
& Richard T. Swank11
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 2
Human Medical Genetics Program, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. 3
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA. 4
The Jackson Laboratory, Bar Harbor, Maine, USA. 5
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, USA. 6
Klinik für Pädiatrische Hämatologie und Onkologie, Heinrich-Heine-Universität, Düsseldorf, Germany. 7
Center for Human Genetics, Universitaire Ziekenhuizen Leuven, Leuven, Belgium. 8
Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland, USA. 9
These authors contributed equally to this work.
Correspondence should be addressed to Richard T. Swank richard.swank@roswellpark.org Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles.
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