Our group identified the gene that causes camptodactyly-arthropathy-coxa vara-pericarditis syndrome in humans (Marcelino, et al., Nature Genetics). We have recently consturcted an animal model for CACP in the form of a knockout mouse. Upon confirmation of the germline transmission of the knockout construct, timed matings were performed on heterozygous mice to test for the presence of synovial hyperplasia in homozygous knockout mice. Knee joints were harvested from sacrificed homozygous knockout mice at different stages in development (15 day, 30 day, 45 day, 60 day, 6 months and 7 months). Hematoxylin-eosin stained sections of knee joints were analyzed for the presence of synovial hyperplasia as compared to age matched heterozygous and normal mice. Synovial hyperplasia was evident as early as 15 days in both outbred and inbred mice. Age was directly proportional to severity of hyperplasia, with invasion of hyperplasic synoviocytes into articular cartilage in 6 and 7 month old mice. Homozygous knockout mice also have presented with pericarditis. Several cases of camptodactyly have been seen in homozygous knockout mice. Heterozygous mice as old as age 9 months showed no obvious phenotype. The CACP knockout mouse model should help us better understand the involvement of Proteoglycan 4 in normal joint function.
