#4181 THE AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE PROTEIN, FPC, RELEASES MITOCHONDRIA LOCALISING FRAGMENTS INVOLVED IN PREVENTING CYSTOGENESIS
نویسندگان
چکیده
Abstract Background and Aims Autosomal recessive polycystic kidney disease is caused by mutations in PKHD1 encoding FPC, characterized severe renal cystogenesis neonates, yet mouse models do not fully recapitulate the human phenotype. Indeed, even Pkhd1 null allele does cause mouse. Several cleavage products of FPC are reported their function remains unknown. The aim this study was to determine effects on cyst development ARPKD. Method Three mutant lines cystic Pkd1V were crossed produce digenic mice with which cystogenesis. Biochemical analysis used investigate patterns using a panel new antibodies. Cell electron microscopy revealed underlying mitochondrial defects Knockout mice. Results mutation modifies Pkd1 uncleavable (Pkd1V), enhancing phenotype both pancreas. hypomorphic KO enhance phenotype, making distal tubule cysts more initiating proximal tubules. displays differential fragments unknown function. New antibodies generated interrogate products. small C terminal identified contain targeting sequence recruited mitochondria. Mitochondrial ultrastructural changes evident after deletion including fragmentation dilated cristae, suggesting disrupted Deletion just C-terminal fragment (ΔCT), portion that directly corresponds cleaves localises mitochondria, sufficient PC1 mutant. Unlike other mutants however, (ΔCT) result pancreatic when combined Pkd1V, terminus required prevent development. Conclusion Our results suggest C-terminus plays an important role preventing via newly discovered mitochondria specific work reveal some aspects FPC's function, particular previously unrecognised mediated through essential enhancement model.
منابع مشابه
Autosomal Recessive Polycystic Kidney Disease
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objecti...
متن کاملAutosomal Recessive Polycystic Kidney Disease
A single gene defect leads to differing degrees of renal and hepatic involvement, with very different phenotypes and clinical outcome within even one affected family. [2] Kidneys are bilaterally enlarged and contain large numbers of cysts throughout the organ, due to the dilatation and elongation of renal collecting ducts. At birth, the interstitium and the rest of the tubules are normal but th...
متن کاملAutosomal Recessive Polycystic Kidney Disease
A 25-year-old pregnant female reported at 28 weeks of gestation with non specific abdominal pain. On evaluation, the ultra-sonogram revealed a single live fetus in breech presentation. Placenta was anterior and high and there was severe oligohydramnios. Both fetal kidneys were enlarged in size (occupying most of the abdominal cavity) and homogenously hyperechoic & studded with numerous variable...
متن کاملAutosomal Recessive Polycystic Kidney Disease
A single gene defect leads to differing degrees of renal and hepatic involvement, with very different phenotypes and clinical outcome within even one affected family. [2] Kidneys are bilaterally enlarged and contain large numbers of cysts throughout the organ, due to the dilatation and elongation of renal collecting ducts. At birth, the interstitium and the rest of the tubules are normal but th...
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ژورنال
عنوان ژورنال: Nephrology Dialysis Transplantation
سال: 2023
ISSN: ['1460-2385', '0931-0509']
DOI: https://doi.org/10.1093/ndt/gfad063a_4181