GENOMIC ORGANIZATION OF THE HUMAN TISSUE INHIBITOR OF METALLOPROTEINASES-3 (TIMP3)

The tissue inhibitors of metalloproteinases (TIMPs) play a crucial rol e in the physiological turnover of the extracellular matrix (ECM) by t ightly regulating matrix metalloproteinase (MMP) activities. Disturban ces in the TIMP/MMP system have been implicated in many disease proces ses where loss of ECM integrity is a principal feature. More recently, we have shown that mutations in TIMP3 cause the autosomal dominant di sorder Sorsby's fundus dystrophy (SFD). This is a macular degeneration disorder with characteristic ECM irregularities in Bruch's membrane. To further facilitate mutational analysis and to provide a basis for f unctional studies, we now report the genomic organization of the human TIMP3 gene.