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U.S.A."],"published-print":{"date-parts":[[2000,7,5]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>dilute<\/jats:italic>\n                    (\n                    <jats:italic>d<\/jats:italic>\n                    ),\n                    <jats:italic>leaden<\/jats:italic>\n                    (\n                    <jats:italic>ln<\/jats:italic>\n                    ), and\n                    <jats:italic>ashen<\/jats:italic>\n                    (\n                    <jats:italic>ash<\/jats:italic>\n                    ) mutations provide a unique model system for studying vesicle transport in mammals. All three mutations produce a lightened coat color because of defects in pigment granule transport. In addition, all three mutations are suppressed by the semidominant\n                    <jats:italic>dilute-suppressor<\/jats:italic>\n                    (\n                    <jats:italic>dsu<\/jats:italic>\n                    ), providing genetic evidence that these mutations function in the same or overlapping transport pathways. Previous studies showed that\n                    <jats:italic>d<\/jats:italic>\n                    encodes a major vesicle transport motor, myosin-VA, which is mutated in Griscelli syndrome patients. Here, using positional cloning and bacterial artificial chromosome rescue, we show that\n                    <jats:italic>ash<\/jats:italic>\n                    encodes\n                    <jats:italic>Rab27a<\/jats:italic>\n                    . Rab GTPases represent the largest branch of the p21 Ras superfamily and are recognized as key players in vesicular transport and organelle dynamics in eukaryotic cells. We also show that\n                    <jats:italic>ash<\/jats:italic>\n                    mice have platelet defects resulting in increased bleeding times and a reduction in the number of platelet dense granules. These defects have not been reported for\n                    <jats:italic>d<\/jats:italic>\n                    and\n                    <jats:italic>ln<\/jats:italic>\n                    mice. Collectively, our studies identify\n                    <jats:italic>Rab27a<\/jats:italic>\n                    as a critical gene for organelle-specific protein trafficking in melanocytes and platelets and suggest that\n                    <jats:italic>Rab27a<\/jats:italic>\n                    functions in both MyoVa dependent and independent pathways.\n                  <\/jats:p>","DOI":"10.1073\/pnas.140212797","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"7933-7938","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":356,"title":["A mutation in\n                    <i>Rab27a<\/i>\n                    causes the vesicle transport defects observed in\n                    <i>ashen<\/i>\n                    mice"],"prefix":"10.1073","volume":"97","author":[{"given":"Scott M.","family":"Wilson","sequence":"first","affiliation":[{"name":"Mouse Cancer Genetics Program, National Cancer Institute\u2013Frederick Cancer Research and Development Center, Frederick, MD 21702; Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Buffalo, NY 14263; and Biology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Yip","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, National Cancer Institute\u2013Frederick Cancer Research and Development Center, Frederick, MD 21702; Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Buffalo, NY 14263; and Biology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Swing","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, National Cancer Institute\u2013Frederick Cancer Research and Development Center, Frederick, MD 21702; Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Buffalo, NY 14263; and Biology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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