biostudies-literatureGetwan MSwiss National Science FoundationDeutsche ForschungsgemeinschaftHHS | NIH | National Institute of Diabetes and Digestive and Kidney DiseasesEC | Horizon 2020e2106770118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8488674biostudies-literatureUnknown118(39)Skeletal ciliopathies (e.g., Jeune syndrome, short rib polydactyly syndrome, and Sensenbrenner syndrome) are frequently associated with nephronophthisis-like cystic kidney disease and other organ manifestations. Despite recent progress in genetic mapping of causative loci, a common molecular mechanism of cartilage defects and cystic kidneys has remained elusive. Targeting two ciliary chondrodysplasia loci (ift80 and ift172) by CRISPR/Cas9 mutagenesis, we established models for skeletal ciliopathies in Xenopus tropicalis Froglets exhibited severe limb deformities, polydactyly, and cystic kidneys, closely matching the phenotype of affected patients. A data mining-based in silico screen found ttc30a to be related to known skeletal ciliopathy genes. CRISPR/Cas9 targeting replicated limb malforProceedings of the National Academy of Sciences of the United States of AmericaTtc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polycystic kidney disease.PMC8488674310030_189102/1Li 1817/2-1NCCR Kidney.CH754825431984000310030192904750KO 3598-5/1189102390939984R01DK068306Hoppmann AHildebrandt FDiehl RLausch EKottgen AGetwan MDeutsch KSchlosser PLienkamp SSGrand KSchroda SSong WHeeg FfalseTtc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polycystic kidney disease.Skeletal ciliopathies (e.g., Jeune syndrome, short rib polydactyly syndrome, and Sensenbrenner syndrome) are frequently associated with nephronophthisis-like cystic kidney disease and other organ manifestations. Despite recent progress in genetic mapping of causative loci, a common molecular mechanism of cartilage defects and cystic kidneys has remained elusive. Targeting two ciliary chondrodysplasia loci (ift80 and ift172) by CRISPR/Cas9 mutagenesis, we established models for skeletal ciliopathies in Xenopus tropicalis Froglets exhibited severe limb deformities, polydactyly, and cystic kidneys, closely matching the phenotype of affected patients. A data mining-based in silico screen found ttc30a to be related to known skeletal ciliopathy genes. CRISPR/Cas9 targeting replicated limb malfor2021-01-01T00:00:00Z2021 Sep2025-04-18T15:40:45.017Z2025-04-07T02:24:19.781ZS-EPMC84886743454839810.1073/pnas.2106770118