Researchers create mouse lacking key inflammation gene
Will likely lead to new treatments for inflammatory disorders
(Boston) -- In a paper published yesterday in The Proceedings of the National Academy of Science (PNAS), researchers from Boston University School of Dental Medicine generated a mouse model exhibiting reduced inflammation.
The Boston University researchers found that the transcription factor LITAF (Lipopolysaccharide [LPS]-Induced TNF-Alpha Factor) controls inflammation through a completely different pathway than the better known and studied NF-kB transcriptional regulator.
Drugs regulating TNF-alpha through the better-known NF-kB pathway such as Remicade, Embrel, and Humira represent a multibillion market. The LITAF transcription factor offers a new approach to treating inflammatory disorders along with other immunological conditions. Researchers are offering this in vivo model for sale to spearhead discovery of drugs against inflammatory disorders such as arthritis and Crohn's disease.
In the study, Boston University researchers created a mouse lacking the gene that encodes for the LITAF protein. They found that several cytokines were induced at lower levels in the LITAF-deficient mice compared with the levels observed in the LITAF-positive control mice. Specifically, the deficient mice were more resistant to LPS-induced lethality.
"The generation of the macrophage-specific LITAF-deficient animals opens new opportunities for assessing the role of LITAF in inflammation in hopes of designing anti-LITAF drugs for major inflammatory diseases," says Dr. Salomon Amar of Boston University, the lead author of the paper. Amar discovered the LITAF transcription factor in 1999.
Researchers, who have applied to patent the mouse, are now working on whether other molecules work in synergy with LITAF.
The paper, "Macrophage-specific LITAF-deficient mice express reduced LPS-induced cytokine profiling: further evidence for LITAF-dependent LPS signaling pathways," by Xiaoren Tang, Daniel Metzger, Susan E. Leeman, and Salomon Amar, may be found here as an abstract (http://www.pnas.org/cgi/content/abstract/0605988103v1?maxtoshow=&HITS=2&hits=2&RESULTFORMAT=&titleabstract=TNF+or+LPS+or+atherosclerosis&andorexacttitleabs=or&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct) or pdf (http://www.pnas.org/cgi/reprint/0605988103v1?maxtoshow=&HITS=2&hits=2&RESULTFORMAT=&titleabstract=TNF+or+LPS+or+atherosclerosis&andorexacttitleabs=or&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct)
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
Published on PsychCentral.com. All rights reserved.