Our congenic breeding was successful in identifying a QTL associated with the development of spontaneous arthritis. When a fragment of DNA from the DBA/1 strain was introduced onto a BALB/c background, arthritis was delayed in onset and was less severe. The congenic strains provide a unique tool for evaluating specific genetic factor/s that regulates the spontaneous onset of spontaneous arthritis. The genetic mapping of QTL using a F2 population, especially with a relatively small population, usually identifies approximate locations of genetic loci for a complex trait. Using the congenic strains that we developed, the genomic region of the originally identified QTL has been redefined into a region that is downstream from the peak region of our original mapping. In our previous study, in our F2 mapping we used 137 microsatellite markers with initially 191 F2 and then 561 F2 mice. Within the 561 F2 population, there is sex ratio of 1:2 between male and female. This data emphasizes the importance of confirmation of QTL regions using additional breeding techniques including the development of congenic strains or other approaches. Understanding the molecular mechanisms underlying the phenotype of the congenic strains has two potentially profound AbMole Ellipticine consequences. First, it may enable us to identify novel pathways that contribute to the development of inflammatory arthritis. It has been recognized that IL-1 signaling is a key component of many forms of human inflammatory arthritis, in the development of joint erosions, and in development of osteoporosis. This data suggests that these cytokines may be coordinately regulated by genes within the QTL but further work will be needed to determine the 
specific pathways involved. Study of the molecular basis of this QTL may identify a complementary approach to what is the most widely implemented biologic therapy for inflammatory arthritis in humans. Although we have not yet identified the causal gene/s within the QTL, those genes with polymorphisms and differential expression levels between BALB/c and DBA/1 deserve detailed examination in the future. The mouse model in this study has important implications for understanding rheumatoid arthritis in humans and potentially other human diseases. Liver fibrosis is a dominant medical problem with significant morbidity and mortality. The most commonly associated characteristic of fibrosis is excessive deposition of extracellular matrix proteins, including glycoprotein, collagens and proteoglycan. The excess deposition of ECM proteins disrupts the normal architecture and functions of the liver. Transforming growth factor b has been recognized as a most potent fibrogenic cytokine, which stimulates the synthesis and deposition of ECM components. After binding to the constitutively active type II receptor, TGF-b stimulates the Smad2/3 signaling by phosphorylating the type I receptor, which ultimately leads to liver cirrhosis, an end-stage consequence of fibrosis.