| http://purl.uniprot.org/citations/23454480 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23454480 | http://www.w3.org/2000/01/rdf-schema#comment | "Meckel-Gruber syndrome (MKS) is an embryonic lethal ciliopathy resulting from mutations in genes encoding proteins localising to the primary cilium. Mutations in the basal body protein MKS1 account for 7% of cases of MKS. The condition affects the development of multiple organs, including brain, kidney and skeleton. Here we present a novel Mks1(tm1a(EUCOMM)Wtsi) knockout mouse which accurately recapitulates the human condition, consistently developing pre-axial polydactyly, complex posterior fossa defects (including the Dandy-Walker malformation), and renal cystic dysplasia. TOPFlash Wnt reporter assays in mouse embryonic fibroblasts (MEFs) showed general de-regulated high levels of canonical Wnt/β-catenin signalling in Mks1(-/-) cells. In addition to these signalling defects, we also observed ectopic high proliferation in the brain and kidney of mutant animals at mid-to late-gestation. The specific role of Mks1 in regulating cell proliferation was confirmed in Mks1 siRNA knockdown experiments which showed increased levels of proliferation after knockdown, an effect not seen after knockdown of other ciliopathy genes. We suggest that this is a result of the de-regulation of multiple signalling pathways (Wnt, mTOR and Hh) in the absence of functional Mks1. This novel model system offers insights into the role of MKS1 in Wnt signalling and proliferation, and the impact of deregulation of these processes on brain and kidney development in MKS, as well as expanding our understanding of the role of Mks1 in multiple signalling pathways."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ydbio.2013.02.015"xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/author | "Johnson C.A."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/author | "Wheway G."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/author | "Toomes C."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/author | "Natarajan S."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/author | "Inglehearn C."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/author | "Abdelhamed Z."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/name | "Dev Biol"xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/pages | "55-66"xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/title | "Aberrant Wnt signalling and cellular over-proliferation in a novel mouse model of Meckel-Gruber syndrome."xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://purl.uniprot.org/core/volume | "377"xsd:string |
| http://purl.uniprot.org/citations/23454480 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23454480 |
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