Send to

Choose Destination
Immunity. 1999 Mar;10(3):387-98.

Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies.

Author information

Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece.


We addressed the impact of deleting TNF AU-rich elements (ARE) from the mouse genome on the regulation of TNF biosynthesis and the physiology of the host. Absence of the ARE affected mechanisms responsible for TNF mRNA destabilization and translational repression in hemopoietic and stromal cells. In stimulated conditions, TNF ARE were required both for the alleviation and reinforcement of message destabilization and translational silencing. Moreover, the mutant mRNA was no longer responsive to translational modulation by the p38 and JNK kinases, demonstrating that TNF ARE are targets for these signals. Development of two specific pathologies in mutant mice, i.e., chronic inflammatory arthritis and Crohn's-like inflammatory bowel disease, suggests that defective function of ARE may be etiopathogenic for the development of analogous human pathologies.

[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center