Tuberous sclerosis complex (TSC) is a genetic disorder characterised by hamartomatous growth abnormalities in many organs. Epilepsy and mental retardation, typical skin manifestations, intracerebral hamartoma, renal angiomyolipoma, and pulmonary lymphangioleiomyomatosis are among the major diagnostic features of TSC. TSC is thought to affect approximately 1 in every 6000 newborns. It has an aut...

OBJECTIVE Histone acetylation/deacetylation plays an important role in the control of gene expression, tissue growth, and development. In particular, histone deacetylases 7 (HDAC7), a member of class IIa HDACs, is crucial in maintaining vascular integrity. However, whether HDAC7 is involved in the processes of vascular endothelial signaling and angiogenesis remains unclear. Here, we investigate...

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the USA resulting in chronic kidney disease and the need for dialysis and transplantation. Approximately 85% of cases of ADPKD are caused by a mutation in the Pkd1 gene that encodes polycystin-1, a large membrane receptor. The Pkd1 gene mutation results in abnormal proliferation in tub...

Interaction of polycystin-1 (PC1) and Gα12 is important for development of kidney cysts in autosomal dominant polycystic kidney disease (ADPKD). The integrity of cell polarity and cell-cell adhesions (mainly E-cadherin-mediated adherens junction) is altered in the renal epithelial cells of ADPKD. However, the key signaling pathway for this alteration is not fully understood. Madin-Darby canine ...

Specification of the mammalian left–right (L–R) axis is controlled by fluid flows in the embryonic node, a ciliated pit like structure located at the distal tip of the mouse embryo. Nodal cilia rotate so as to cause a leftward fluid flow-this has been experimentally demonstrated to control embryonic sidedness. How the embryo interprets this flow remains the subject of debate. The two cilia hypo...

Specification of the mammalian left–right (L–R) axis is controlled by fluid flows in the embryonic node, a ciliated pit like structure located at the distal tip of the mouse embryo. Nodal cilia rotate so as to cause a leftward fluid flow-this has been experimentally demonstrated to control embryonic sidedness. How the embryo interprets this flow remains the subject of debate. The two cilia hypo...

A "two-hit" hypothesis predicts a second somatic hit, in addition to the germline mutation, as a prerequisite to cystogenesis and has been proposed to explain the focal nature for renal cyst formation in autosomal dominant polycystic kidney disease (ADPKD). It was reported previously that Pkd1(null/null) mouse kidney epithelial cells are unresponsive to flow stimulation. This report shows that ...

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic disease predominantly caused by alteration or dysregulation of the PKD1 gene, which encodes polycystin-1 (PC1). The disease is characterized by the progressive expansion of bilateral fluid-filled renal cysts that ultimately lead to renal failure. Individual cysts, even within patients with germline mutations, ar...

establish ultrasonographic criteria in patients who have unknown genotype and are at risk for ADPKD. Moreover, the results demonstrate that the diagnostic criteria currently in use for PKD1 may be inaccurate when applied to PKD2 because of higher risks for false-negative results yielding a reduced sensitivity for individuals aged 15 to 59. In summary, the authors propose new ultrasound diagnost...

Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome in which severe renal cystic disease can occur. Many renal cystic diseases, including autosomal dominant polycystic kidney disease (ADPKD), are associated with absence or dysfunction of the primary cilium. We report here that hamartin (TSC1) localizes to the basal body of the primary cilium, and that Tsc1(-/-) and Tsc2(-/-) mo...