Sternal cartilage microarray (WT vs. TIMPless)

Timps are natural metalloproteinase inhibitors that direct the cell microenvironment in health and disease, yet the essential requirement of this gene family in mammals is unknown. We generated quadruple Timp deficient mice lacking Timp1, Timp2, Timp3 and Timp4 (TIMPless) and found that Timp function is essential for postnatal lifespan, lung form and function and skeletogenesis. TIMPless mice survive embryogenesis but develop pervasive skeletal aberrations characterized by axial cartilage overgrowth and growth plate closure in long bones. We performed microarray analysis to identify signaling pathways affected by the loss of the entire Timp family in sternal cartilage. Cartilage, excluding the xiphoid process, was macrodissected from the sternums of 4-week old WT and TIMPless mice (n=6/genotype).