A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency.

Published

Journal Article

Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TTP by gene targeting appeared normal at birth, but soon manifested marked medullary and extramedullary myeloid hyperplasia associated with cachexia, erosive arthritis, dermatitis, conjunctivitis, glomerular mesangial thickening, and high titers of anti-DNA and antinuclear antibodies. Myeloid progenitors from these mice showed no increase in sensitivity to growth factors. Treatment of young TTP-deficient mice with antibodies to tumor necrosis factor alpha (TNF alpha) prevented the development of essentially all aspects of the phenotype. These results indicate a role for TTP in regulating TNF alpha synthesis, secretion, turnover, or action. TTP-deficient mice may serve as useful models of the autoimmune inflammatory state resulting from chronic effective TNF alpha excess.

Full Text

Duke Authors

Cited Authors

  • Taylor, GA; Carballo, E; Lee, DM; Lai, WS; Thompson, MJ; Patel, DD; Schenkman, DI; Gilkeson, GS; Broxmeyer, HE; Haynes, BF; Blackshear, PJ

Published Date

  • May 1996

Published In

Volume / Issue

  • 4 / 5

Start / End Page

  • 445 - 454

PubMed ID

  • 8630730

Pubmed Central ID

  • 8630730

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(00)80411-2

Language

  • eng

Conference Location

  • United States