Loss of a single allele of SHIP exacerbates the immunopathology of Pten heterozygous mice
| Autor: | A Magil, C G Pereira, J L Moody, F R Jirik, M J Fritzler |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Immunology
Phosphatase Loss of Heterozygosity Biology Kidney Loss of heterozygosity chemistry.chemical_compound Mice Immune system Immunopathology Genetics PTEN Animals Inositol Phosphatidylinositol Lymphatic Diseases Genetics (clinical) PI3K/AKT/mTOR pathway Cells Cultured Genetic Carrier Screening Tumor Suppressor Proteins PTEN Phosphohydrolase Mice Mutant Strains Phosphoric Monoester Hydrolases chemistry Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases Cancer research biology.protein Female Spleen |
| Zdroj: | Genes and immunity. 4(1) |
| ISSN: | 1466-4879 |
| Popis: | Phosphatidylinositol 3-kinase (PI3K) has emerged as a critical component of multiple immune system intracellular signalling pathways. The levels and relative ratios of PI3K products, phosphatidylinositol (3,4) bisphosphate (PI(3,4)P(2)) and phosphatidylinositol (3,4,5) trisphosphate (PIP(3)), are regulated by inositol phosphatases such as Pten and SHIP. Interestingly, mice heterozygous for Pten, a 3'-inositol phosphatase, develop a progressive lymphoproliferative syndrome with autoimmune features. Given the importance of PIP(3) species in regulating immune responses, we hypothesized that heterozygosity for the 5'-inositol phosphatase SHIP might exacerbate the autoimmune phenotype of Pten(+/-) mice. In keeping with this, mice heterozygous for both Pten and SHIP developed lymphoproliferation, hypergammaglobulinaemia, autoantibody titres and renal pathology that were more severe than that of Pten(+/-) mice. These results suggest that the relative levels of phosphatidylinositol phosphatases are likely critical to immune system homeostasis and they also highlight the potential for gene dosage effects in regulating susceptibility and/or severity of autoimmunity. |
| Databáze: | OpenAIRE |
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