Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6.
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.
Zhang
Qing
Q
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Zhao
Baohui
B
Li
Wei
W
Oiso
Naoki
N
Novak
Edward K
EK
Rusiniak
Michael E
ME
Gautam
Rashi
R
Chintala
Sreenivasulu
S
O'Brien
Edward P
EP
Zhang
Yuke
Y
Roe
Bruce A
BA
Elliott
Rosemary W
RW
Eicher
Eva M
EM
Liang
Ping
P
Kratz
Christian
C
Legius
Eric
E
Spritz
Richard A
RA
O'Sullivan
T Norene
TN
Copeland
Neal G
NG
Jenkins
Nancy A
NA
Swank
Richard T
RT
D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019476:Insect Proteins / Q000235:genetics*; D008297:Male; D020460:Melanosomes / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009842:Oligopeptides; D010455:Peptides / Q000276:immunology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020798:Two-Hybrid System Techniques
C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D033942:Adaptor Proteins, Vesicular Transport; D029721:Drosophila Proteins; C102160:HPS1 protein, human; C491131:Hps1 protein, mouse; D019476:Insect Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009842:Oligopeptides; D010455:Peptides; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; C410303:RB protein, Drosophila; C085706:FLAG peptide