Finally, there are ongoing efforts to harness the therapeutic potential of m Iproniazid phosphate conotoxins by designing analogues that selectively bind to a target NaV1 channel. Construction of accurate models of NaV1�C m conotoxin complexes will be very useful in such efforts. Regardless, our findings emphasize the importance of thorough monitoring of OI patients for non-skeletal consequences of their connective tissue disease. For instance, renal abnormalities are reported in OI patients that may not be detected without monitoring. In one series, 17 out of 47 Probucol individuals with OI had persistent hypercalciuria, correlating with severity of the OI, with one patient having isolated microscopic hematuria ; in a separate study 4 out of 58 OI children were found with nephrolithiasis. It is likely that the large majority of these OI cases are due to mutations in the type I collagen genes, but it is unclear if the OI caused by CRTAP, LEPRE1, orPPIB mutations may also have renal abnormalities. Furthermore, it must be acknowledged that the hypercalciuria may be secondary to abnormal bone mineral metabolism, although our results suggest that a primary kidney defect should also be considered. Regardless, because individuals with OI are often supplemented with vitamin D and calcium, which are known to increase calcium flux in the kidney, it is especially important for the treating physician to be attentive to any renal complications. Glomerulopathy has been observed in another mouse model of osteogenesis imperfecta, the homotrimeric a1 collagen oim/oim mouse, suggesting that distinct molecular abnormalities in OI can result in a similar skeletal and extraskeletal phenotype. The subtle nature of this abnormality is confirmed by the absence of proteinuria by dipstick analysis in both our Crtap-/- mice and in the OI patients with hypercalciuria, as well as the normal levels of serum and urinary calcium, phosphorous, and magnesium previously reported in the Crtap-/- mice. The most common causes of death in individuals with severe OI are respiratory problems, including pneumonia.