Disregulated production of TNF is implicated in many diseases such as arthritis and multiple sclerosis. Evidence is emerging that TNF acts via different mechanisms depending on whether the transmembrane or soluble molecular form is the activating molecule. Previously a transmembrane TNF model has been developed, but no corresponding soluble TNF model is available.
It is therefore proposed to create such transgenic animals and to use them to assess the individual contribution of each form of TNF in immune functioning. It is also proposed to create TNF mutant mice where either soluble or trasmembrane TNF is expressed in the absence of endogenous TSF. It is also proposed to create targeted mutants where expression is directed to either the T cell or macrophage cells using previously defined cell specific modifiers of expression such as the CD2 LCR known to target T cell specific expression.