• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

The Slc35d3 gene, encoding an orphan nucleotide sugar transporter, regulates platelet-dense granules.

Platelet dense granules are lysosome-related organelles which contain high concentrations of several biologically important low-molecular-weight molecules. These include calcium, serotonin, adenine nucleotides, pyrophosphate, and polyphosphate, which are necessary for normal blood hemostasis. The synthesis of dense granules and other lysosome-related organelles is defective in inherited diseases such as Hermansky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS). HPS and CHS mutations in 8 human and at least 16 murine genes have been identified. Previous studies produced contradictory findings for the function of the murine ashen (Rab27a) gene in platelet-dense granules. We have used a positional cloning approach with one line of ashen mutants to establish that a new mutation in a second gene, Slc35d3, on mouse chromosome 10 is the basis of this discrepancy. The platelet-dense granule defect is rescued in BAC transgenic mice containing the normal Slc35d3 gene. Thus, Slc35d3, an orphan member of a nucleotide sugar transporter family, specifically regulates the contents of platelet-dense granules. Unlike HPS or CHS genes, it has no apparent effect on other lysosome-related organelles such as melanosomes or lysosomes. The ash-Roswell mouse mutant is an appropriate model for human congenital-isolated delta-storage pool deficiency.

Pubmed ID: 17062724

Authors

  • Chintala S
  • Tan J
  • Gautam R
  • Rusiniak ME
  • Guo X
  • Li W
  • Gahl WA
  • Huizing M
  • Spritz RA
  • Hutton S
  • Novak EK
  • Swank RT

Journal

Blood

Publication Data

February 15, 2007

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR39892
  • Agency: NEI NIH HHS, Id: EY-12104
  • Agency: NEI NIH HHS, Id: EY015626
  • Agency: NHLBI NIH HHS, Id: HL-31698
  • Agency: NHLBI NIH HHS, Id: HL-51480

Mesh Terms

  • Animals
  • Blood Platelets
  • Chromosome Mapping
  • Chromosomes, Mammalian
  • Cytoplasmic Granules
  • Lysosomes
  • Mice
  • Mice, Transgenic
  • Monosaccharide Transport Proteins
  • Mutation
  • rab GTP-Binding Proteins