SIRPα polymorphisms, but not the prion protein, control phagocytosis of apoptotic cells

Mario Nuvolone, Veronika Kana, Gregor Hutter, Daiji Sakata, Steven M. Mortin-Toth, Giancarlo Russo, Jayne S. Danska, Adriano Aguzzi

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2539-2552
Number of pages14
JournalJournal of Experimental Medicine
Issue number12
Publication statusPublished - Nov 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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