SIRPα polymorphisms, but not the prion protein, control phagocytosis of apoptotic cells
| Autor: | Steven M. Mortin-Toth, Giancarlo Russo, Mario Nuvolone, Daiji Sakata, Gregor Hutter, Jayne S. Danska, Adriano Aguzzi, Veronika Kana |
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| Přispěvatelé: | University of Zurich, Aguzzi, Adriano |
| Rok vydání: | 2013 |
| Předmět: |
Male
Mice 129 Strain Prions Phagocytosis animal diseases Immunology Molecular Sequence Data 10208 Institute of Neuropathology 610 Medicine & health 10071 Functional Genomics Center Zurich Apoptosis Biology Polymorphism Single Nucleotide Prion Proteins Article PRNP Apoptotic cell clearance 03 medical and health sciences Mice 0302 clinical medicine mental disorders Immunology and Allergy Animals Humans Amino Acid Sequence Receptors Immunologic Receptor Gene 030304 developmental biology Regulation of gene expression Mice Knockout 2403 Immunology 0303 health sciences Mice Inbred BALB C Polymorphism Genetic Sequence Homology Amino Acid Molecular biology Phenotype humanities nervous system diseases 2723 Immunology and Allergy Macrophages Peritoneal 570 Life sciences biology Female 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Experimental Medicine JOURNAL OF EXPERIMENTAL MEDICINE Journal of Experimental Medicine The Journal of experimental medicine |
| ISSN: | 1540-9538 |
| Popis: | The regulation of phagocytosis previously ascribed to prion protein PrPC is found to be controlled by the linked locus encoding SIRPα. Prnp−/− mice lack the prion protein PrPC and are resistant to prion infections, but variable phenotypes have been reported in Prnp−/− mice and the physiological function of PrPC remains poorly understood. Here we examined a cell-autonomous phenotype, inhibition of macrophage phagocytosis of apoptotic cells, previously reported in Prnp−/− mice. Using formal genetic, genomic, and immunological analyses, we found that the regulation of phagocytosis previously ascribed to PrPC is instead controlled by a linked locus encoding the signal regulatory protein α (Sirpa). These findings indicate that control of phagocytosis was previously misattributed to the prion protein and illustrate the requirement for stringent approaches to eliminate confounding effects of flanking genes in studies modeling human disease in gene-targeted mice. The plethora of seemingly unrelated functions attributed to PrPC suggests that additional phenotypes reported in Prnp−/− mice may actually relate to Sirpa or other genetic confounders. |
| Databáze: | OpenAIRE |
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