Sirpa Conditional Knockout mouse models

Encoding signal regulatory protein alpha (CD172a), Sirpa is the mouse ortholog of human SIRPA and presents three extracellular immunoglobulin domains, of which the polymorphic IgV domain binds CD47, plus a cytoplasmic tail with two ITIMs that recruit SHP-1 and SHP-2 to block phagocytic cup maturation and myosin IIA accumulation in macrophages, neutrophils, and dendritic cells. This CD47 to SIRPA axis is the dominant myeloid checkpoint that tumors exploit, and it is under strong species constraint because mouse SIRPA binds human CD47 poorly, which is exactly why humanized IgV knockin strains greatly improve human hematopoietic engraftment in immunodeficient hosts. Design forks sharply: conditional nulls or cytoplasmic truncations test ITIM-dependent inhibition in a defined myeloid lineage, whereas full ectodomain humanization is mandatory for anti-SIRPA or CD47 blocking antibodies and xenograft work. Related Sirpb1 and Sirpg do not restore inhibitory signaling, so target red cell clearance, antibody-dependent phagocytosis, or engraftment endpoints.

A floxed Sirpa allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.