B. Richards-smith et al., Analyses of proteins involved in vesicular trafficking in platelets of mouse models of Hermansky Pudlak syndrome, MOL GEN MET, 68(1), 1999, pp. 14-23
Hermansky Pudlak syndrome (HPS) is an autosomal recessive inherited disorde
r characterized by defects in synthesis and/or secretion of three related s
ubcellular organelles: melanosomes, platelet-dense granules, and lysosomes.
In the mouse, mutant forms of any of 14 separate genes result in an HPS-li
ke phenotype. The mouse pearl and mocha genes encode subunits of the AP3 ad
aptor protein complex, confirming that HPS mutations involve proteins regul
ating intracellular vesicular trafficking. Therefore, expression of several
additional proteins involved in vesicular transport was examined by immuno
blotting of platelet extracts from HPS mutant and control mice. Platelet le
vels of SCAMPS (secretory carrier membrane proteins), Rab11, Rab81, NSF (N-
ethylmaleimide-sensitive fusion protein), syntaxin 2, syntaxin 4, munc18c,
and p115/TAP (p115/transcytosis-associated protein) were not significantly
altered in several different HPS mutants. However, gunmetal (gm/gm) platele
ts contained decreased amounts of SNAP-23. The Snap23 gene was mapped to mo
use chromosome 5, demonstrating it cannot encode the gm gene, which maps to
chromosome 14. It is likely therefore that the gm gene functions upstream
of SNAP-23 in vesicular trafficking. (C) 1999 Academic Press.