International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

F3 Positional Cloning of the Pallid Gene Reveals a Novel, Syntaxin 13-Interacting Protein Involved in Platelet Storage Pool Deficiency

Liping Huang1, Yien-Ming Kuo2, and Jane Gitschier,1,2. Howard Hughes Medical Institute1 and Departments of Medicine1 and Pediatrics2 University of California, San Francisco, CA 94143-0794

Pallid (pa) is one of 13 platelet storage pool deficiency (SPD) mouse mutants. Pallid animals suffer from prolonged bleeding time, pigment dilution, kidney lysosomal enzyme elevation, serum a1-antitrypsin activity deficiency, and abnormal otolith formation. As in the other mouse mutants of this class, the constellation of findings in pallid suggests a defect in organelle biosynthesis. In this report, we describe the physical mapping, positional cloning, and mutational and functional analysis of the gene defective in pallid. This gene encodes a ubiquitously expressed, highly charged 172-amino-acid protein (pallidin) with no homology to known proteins. A nonsense mutation was detected at codon 69 of this gene in the pallid mutant. In a yeast two-hybrid screen, pallidin was discovered to interact with syntaxin 13, a t-SNARE protein that mediates vesicle docking and fusion. Syntaxin 13 localizes to the endosomal membrane and is required for vesicle fusion to the early endosomes and recycling endosomes. The interaction was confirmed by co-immunoprecipitation assays. Immunofluorescence studies have shown that the cellular distribution of pallidin overlaps that of syntaxin 13, indicating an endosomal localization of pallidin. Finally, in pallid animals, the level of syntaxin 13 is reduced two-fold compared with C57BL/6J, although the mRNA level is not affected, suggesting that a loss of its pallidin partner could lead to instability of syntaxin 13. Whereas the mocha and pearl SPD mutants have defects in AP-3, our findings suggest that the pallid SPD mutant is defective in a more downstream event in vesicle trafficking, namely vesicle docking and fusion.


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