[PDF][PDF] A pathogenetic role for TNFα in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency

GA Taylor, E Carballo, DM Lee, WS Lai, MJ Thompson… - Immunity, 1996 - cell.com
GA Taylor, E Carballo, DM Lee, WS Lai, MJ Thompson, DD Patel, DI Schenkman…
Immunity, 1996cell.com
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 …
Abstract
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 α (TNFα) prevented the development of essentially all aspects of the phenotype. These results indicate a role for TTP in regulating TNFα synthesis, secretion, turnover, or action. TTP-deficient mice may serve as useful models of the autoimmune inflammatory state resulting from chronic effective TNFα excess.
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