Transgenic analysis of scleroderma: understanding key pathogenic events in vivo
Abstract
Modern molecular genetic methods have allowed better understanding of established mouse models of scleroderma and also facilitated the development of new and better defined mouse strains for investigating the pathogenesis of the disease. The best characterized scleroderma animal model is the type 1 tight skin mouse (Tsk1). Backcrossing these animals with other mutant strains has been informative. These experiments implicate the IL-4 ligand-receptor axis in the development of skin fibrosis. Parallel expression analysis of genes using microarrays has provided insight into novel mediators of fibrosis including the C-C chemokine MCP-3. Other experiments suggest that embryonically defined fibroblast-specific regulatory elements may be targets for activation in this model. The same lineage-specific elements have been used to selectively activate TGF beta signaling pathways in fibrosis to generate a novel model for scleroderma and also have been used to develop systems for ligand-dependent fibroblast-specific genetic recombination that will allow further analysis key candidate genes implicated in scleroderma pathogenesis. Better mouse models will improve understanding of this intractable rheumatic disease and can be expected to ultima...Continue Reading
References
Citations
Related Concepts
Related Feeds
Autoimmune Diseases
Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.
B cells: Gene Expression
B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.