Abnormal fibrillin metabolism in bovine Marfan syndrome.

Bovine Marfan syndrome is a disorder that closely resembles human Marfan syndrome in its clinical signs and pathological lesions. The similarities between the human and bovine diseases suggest that similar metabolic defects could be responsible. Although indirect immunofluorescent assays for fibrillin in skin biopsies did not distinguish affected cattle from control animals, cultures of skin fibroblasts of affected animals were distinguished from normal, unrelated control animals and normal half-siblings on the basis of fibrillin staining. After 72 to 96 hours in culture, stained with anti-fibrillin monoclonal antibody 201, hyperconfluent fibroblast cultures of affected cattle had less immunoreactive fibrillin than control cultures, and the staining pattern was granular rather than fibrillar. Under similar culture conditions, normal bovine aortic smooth muscle cells produced large amounts of immunoreactive fibrillin, but smooth muscle cells from a single affected cow showed markedly less fibrillin staining. In pulse-chase metabolic labeling experiments with [35S]cysteine, dermal fibroblasts from 6 affected calves, incorporated far less fibrillin into the extracellular matrix than control cells. These findings are similar to those reported in human Marfan syndrome, and they suggest that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis.