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Familial polycythemia due to truncations of the erythropoietin receptor.

Publication ,  Journal Article
Forget, BG; Degan, BA; Arcasoy, MO
Published in: Trans Am Clin Climatol Assoc
2000

We studied a kindred with dominantly inherited familial erythrocytosis associated with heterozygosity for a deletion of seven nucleotides in exon 8 of the EpoR gene resulting in an EpoR peptide that is truncated by 59 amino acids in its C-terminal intracytoplasmic signal transduction domain. A seven basepair direct repeat sequence is present in the normal EpoR gene at the site of this mutation, consistent with the slipped mispairing model for the generation of short deletions during DNA replication. Hypersensitivity to erythropoietin of primary erythroid progenitors from an affected individual was observed in in vitro cultures of peripheral blood mononuclear cells, as indicated by the growth, at suboptimal concentrations of added Epo, of more numerous and larger BFU-E-derived erythroid cell colonies compared to those obtained from a normal control subject. To study mutant EpoR function, the cDNA encoding the mutant EpoR was stably transfected into murine growth factor (IL-3)-dependent 32D tissue culture cells. In proliferation assays, cells expressing the mutant EpoR displayed 5 to 10-fold increased sensitivity to Epo compared to cells expressing similar numbers of the wild type EpoR. In addition, the cells transfected with the mutant truncated receptor demonstrated prolonged activity of Jak2 kinase and Stat5 activity, molecules that mediate signal transduction by the EpoR.

Duke Scholars

Published In

Trans Am Clin Climatol Assoc

ISSN

0065-7778

Publication Date

2000

Volume

111

Start / End Page

38 / 44

Location

United States

Related Subject Headings

  • Transfection
  • Trans-Activators
  • Sequence Deletion
  • STAT5 Transcription Factor
  • Receptors, Erythropoietin
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Polycythemia
  • Pedigree
  • Mutation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Forget, B. G., Degan, B. A., & Arcasoy, M. O. (2000). Familial polycythemia due to truncations of the erythropoietin receptor. Trans Am Clin Climatol Assoc, 111, 38–44.
Forget, B. G., B. A. Degan, and M. O. Arcasoy. “Familial polycythemia due to truncations of the erythropoietin receptor.Trans Am Clin Climatol Assoc 111 (2000): 38–44.
Forget BG, Degan BA, Arcasoy MO. Familial polycythemia due to truncations of the erythropoietin receptor. Trans Am Clin Climatol Assoc. 2000;111:38–44.
Forget, B. G., et al. “Familial polycythemia due to truncations of the erythropoietin receptor.Trans Am Clin Climatol Assoc, vol. 111, 2000, pp. 38–44.
Forget BG, Degan BA, Arcasoy MO. Familial polycythemia due to truncations of the erythropoietin receptor. Trans Am Clin Climatol Assoc. 2000;111:38–44.

Published In

Trans Am Clin Climatol Assoc

ISSN

0065-7778

Publication Date

2000

Volume

111

Start / End Page

38 / 44

Location

United States

Related Subject Headings

  • Transfection
  • Trans-Activators
  • Sequence Deletion
  • STAT5 Transcription Factor
  • Receptors, Erythropoietin
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Polycythemia
  • Pedigree
  • Mutation