ABSTRACT
The preceding sections have dealt with the biochemical and biophysical characterization of a gene product thought to be involved in a particular disease process. These approaches may provide valuable insight into disease pathogenesis. However, frequently, the effect of a mutation in a gene can only be determined by study of the gene product in its cellular context. This may be because the gene is only expressed in certain organs or tissues. Alternatively, the nature of any defect in protein function may only be appreciated when the protein is expressed in cells. For example, mutations in the ligand binding domain of the bone morphogenetic protein type II receptor (BMPR-II), which underlie many cases of familial primary pulmonary hypertension,1 would be predicted on the basis of modeling and biochemical studies to lead to reduced ligand binding at the cell surface. In fact, transfection studies in relevant cells have shown that trafficking of these mutants is held up within the endoplasmic reticulum and mutant receptors never attain the cell surface.2
