| http://purl.uniprot.org/citations/21327084 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21327084 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21327084 | http://www.w3.org/2000/01/rdf-schema#comment | "The lamin B receptor (LBR) is an inner nuclear membrane protein with a structural function interacting with chromatin and lamins, and an enzymatic function as a sterol reductase. Heterozygous LBR mutations cause nuclear hyposegmentation in neutrophils (Pelger anomaly), while homozygous mutations cause prenatal death with skeletal defects and abnormal sterol metabolism (Greenberg dysplasia). It has remained unclear whether the lethality in Greenberg dysplasia is due to cholesterol defects or altered nuclear morphology.To answer this question we characterized two LBR missense mutations and showed that they cause Greenberg dysplasia. Both mutations affect residues that are evolutionary conserved among sterol reductases. In contrast to wildtype LBR, both mutations failed to rescue C14 sterol reductase deficient yeast, indicating an enzymatic defect. We found no Pelger anomaly in the carrier parent excluding marked effects on nuclear structure. We studied Lbr in mouse embryos and demonstrate expression in skin and the developing skeletal system consistent with sites of histological changes in Greenberg dysplasia. Unexpectedly we found in disease-relevant cell types not only nuclear but also cytoplasmatic LBR localization. The cytoplasmatic LBR staining co-localized with ER-markers and is thus consistent with the sites of endogeneous sterol synthesis. We conclude that LBR missense mutations can abolish sterol reductase activity, causing lethal Greenberg dysplasia but not Pelger anomaly. The findings separate the metabolic from the structural function and indicate that the sterol reductase activity is essential for human intrauterine development."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.org/dc/terms/identifier | "doi:10.4161/nucl.1.4.12435"xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.org/dc/terms/identifier | "doi:10.4161/nucl.1.4.12435"xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Clayton P."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Clayton P."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Lang C."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Lang C."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Hoffmann K."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Hoffmann K."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Mundlos S."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Mundlos S."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Stricker S."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Stricker S."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Fischer B."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Fischer B."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Mansour S."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Mansour S."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Utermann G."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Utermann G."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Rossier E."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Rossier E."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Sperling K."xsd:string |
| http://purl.uniprot.org/citations/21327084 | http://purl.uniprot.org/core/author | "Sperling K."xsd:string |