Transgenic mouse models to study the physiological and pathophysiological roles of human Siglecs.

Abstract

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are important immunomodulatory receptors. Due to differences between human and mouse Siglecs, defining the in vivo roles for human Siglecs (hSiglecs) can be challenging. One solution is the development and use of hSiglec transgenic mice to assess the physiological roles of hSiglecs in health and disease. These transgenic mice can also serve as important models for the pre-clinical testing of immunomodulatory approaches that are based on targeting hSiglecs. Four general methods have been used to create hSiglec-expressing transgenic mice, each with associated advantages and disadvantages. To date, transgenic mouse models expressing hSiglec-2 (CD22), -3 (CD33), -7, -8, -9, -11, and -16 have been created. This review focuses on both the generation of these hSiglec transgenic mice, along with the important findings that have been made through their study. Cumulatively, hSiglec transgenic mouse models are providing a deeper understanding of the differences between human and mice orthologs/paralogs, mechanisms by which Siglecs regulate immune cell signaling, physiological roles of Siglecs in disease, and different paradigms where targeting Siglecs may be therapeutically advantageous.