| http://purl.uniprot.org/citations/17095521 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17095521 | http://www.w3.org/2000/01/rdf-schema#comment | "Homozygous itchy mice develop a fatal, late-onset autoimmune-like disease due to a loss of function mutation in an ubiquitin protein ligase. Phylogenetic and in vitro analyses suggest that Itch is a negative regulator of Notch signaling. Since Notch proteins have many important functions in the immune system, we determined whether Itch regulates Notch signaling in vivo. This was accomplished by breeding homozygous itch mice to mice carrying an activated Notch1 transgene that was specifically overexpressed in developing thymocytes. Interestingly, all itch mice carrying this transgene were smaller than their littermates and died by 12 weeks of age. These mice had a similar autoimmune disease to that seen in itch animals. However, the lesions were more severe with a much earlier age of onset, supporting the assertion that these mutations genetically interact. In addition, the combination of these mutations produced novel phenotypes including a perturbation in T cell development, with a reduction in the number of double-positive (DP) and an increase in the number of double-negative and single-positive T cells. TUNEL staining showed reduced apoptosis in the thymus of itch animals that carry the Notch1 transgene. Antibody staining displayed increased levels of full-length Notch1 and phospho-AKT specifically in DP thymocytes but no change in other signaling pathways including MAPK, p38 and JNK. These results provide the first direct demonstration that increased AKT-mediated Notch1 signaling results in autoimmunity and may provide insight into the treatment of a group of diseases that affect a significant proportion of the population."xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddl425"xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/author | "Copeland N.G."xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/author | "Jenkins N.A."xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/author | "Haines D.C."xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/author | "Matesic L.E."xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/pages | "3485-3497"xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/title | "Itch genetically interacts with Notch1 in a mouse autoimmune disease model."xsd:string |
| http://purl.uniprot.org/citations/17095521 | http://purl.uniprot.org/core/volume | "15"xsd:string |
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