Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slow progression of multiple cysts in both kidneys that lead to renal insufficiency in mid-life or later. ADPKD is associated with mutations mainly in the PKD1 gene (encoding polycystin-1 or PC1) and less frequently in the PKD2 gene (encoding polycystin-2 or PC2). To mimic naturally occurring human PKD1 mutations and gain ...

Protein kinases are of particular interest in treatment of human diseases because of their enzymatic activity and susceptibility to successful therapeutic targeting. Protein kinase D1 (PKD1), cloned from humans and mouse by two different groups and reported simultaneously in 1990s, is emerging as a protein of translational value. Accumulating evidence in the literature demonstrate that PKD1 pla...

BACKGROUND The homozygous deletion of Pkd1 in the mouse results in embryonic lethality with renal cysts and hydrops fetalis, but there is no precise data on the segmental origin of cysts and potential changes associated with polyhydramnios. METHODS We used Pkd1-null mice to investigate cystogenesis and analyze the amniotic fluid composition from embryonic day 12.5 (E12.5) to birth (n = 257 em...

Characterization of mutations of the PKD1 gene has been limited by the fact that three-fourths of this gene at its 5' end is homologous to sequences of at least three other genes on the same chromosome. We have therefore developed a method of long reverse transcription PCR for selective amplification of the entire coding sequence of the PKD1 gene from its mRNA. A PCR primer specific to the sequ...

Despite their role in resolving inflammatory insults, neutrophils trigger inflammation-induced acute lung injury (ALI), culminating in acute respiratory distress syndrome (ARDS), a frequent complication with high mortality in humans. Molecular mechanisms underlying recruitment of neutrophils to sites of inflammation remain poorly understood. Here, we show that p38 MAP kinase p38δ is required fo...

BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability ...

We have previously shown that PKD1, the gene encoding Polycystin-1 (or TRPP1) is expressed in human odontoblasts and that this protein is localized at the primary cilium of the cell. Nevertheless, its function remain unclear in this cell even if studies on osteoblasts, osteocytes and chondrocytes give TRPP1 as a promising candidate for mechanotransduction in response to mechanical stress. Conse...

The gene for the most common and severe form of autosomal dominant polycystic kidney disease, PKD1, encodes a 14 kb mRNA that is predicted to result in an integral membrane protein of 4302 amino acids. The major challenge faced by researchers attempting to complete mutation analysis of the PKD1 gene has been the presence of several homologous loci also located on chromosome 16. Because the sequ...

Mutations in PKD1 are associated with autosomal dominant polycystic kidney disease. Studies in mouse models suggest that the vasopressin (AVP) V2 receptor (V2R) pathway is involved in renal cyst progression, but potential changes before cystogenesis are unknown. This study used a noncystic mouse model to investigate the effect of Pkd1 haploinsufficiency on water handling and AVP signaling in th...

Tuberous sclerosis(TS) is an autosomal dominant disease caused by mutations in TSC1 and TSC2 genes. TSC2 gene is located in chromosome 16p13.3, adjacent to PKD1 gene, responsible for the autosomal dominant polycystic kidney disease. In a rare subgroup of patients, the presence of a deletion which simultaneously affects the TSC2 and PKD1 genes has been confirmed. TSC2/PKD1-Contiguous Gene Syndro...