Abstract
Cluster of differentiation 47 (CD47) is a member of the immunoglobulin superfamily which functions as a ligand for the extracellular region of signal regulatory protein α (SIRPα), a protein which is abundantly expressed in the brain. Previous studies, including ours, have demonstrated that both CD47 and SIRPα fulfill various functions in the central nervous system (CNS), such as the modulation of synaptic transmission and neuronal cell survival. We previously reported that CD47 is involved in the regulation of depression-like behavior of mice in the forced swim test through its modulation of tyrosine phosphorylation of SIRPα. However, other potential behavioral functions of CD47 remain largely unknown. In this study, in an effort to further investigate functional roles of CD47 in the CNS, CD47 knockout (KO) mice and their wild-type littermates were subjected to a battery of behavioral tests. CD47 KO mice displayed decreased prepulse inhibition, while the startle response did not differ between genotypes. The mutants exhibited slightly but significantly decreased sociability and social novelty preference in Crawley’s three-chamber social approach test, whereas in social interaction tests in which experimental and stimulus mice have direct contact with each other in a freely moving setting in a novel environment or home cage, there were no significant differences between the genotypes. While previous studies suggested that CD47 regulates fear memory in the inhibitory avoidance test in rodents, our CD47 KO mice exhibited normal fear and spatial memory in the fear conditioning and the Barnes maze tests, respectively. These findings suggest that CD47 is potentially involved in the regulation of sensorimotor gating and social behavior in mice.
Highlights
Cluster of differentiation 47 (CD47), referred to as integrinassociated protein (IAP), is a member of the immunoglobulin superfamily possessing a V-type immunoglobulin domain in its extracellular domain, five membrane-spanning domains and a short cytoplasmic tail [1]
There were no significant differences between CD47 KO mice and their wild-type littermates in body weight (Figure 1A; F1,38 = 0.309, p = 0.5814) or body temperature (Figure 1B; F1,38 = 1.216, p = 0.2771)
While the present study revealed that the lack of CD47 did not lead to significant abnormalities in overall health, a few physical and behavioral characteristics were newly identified
Summary
Cluster of differentiation 47 (CD47), referred to as integrinassociated protein (IAP), is a member of the immunoglobulin superfamily possessing a V-type immunoglobulin domain in its extracellular domain, five membrane-spanning domains and a short cytoplasmic tail [1]. SIRPa contains three Ig-like domains in its extracellular region and putative tyrosine phosphorylation sites in its cytoplasmic region [3,4]. CD47 and SIRPa are both highly expressed in synapse-rich regions [2,4,6], and are considered to form a heterophilic complex to mediate bi-directional signaling between cells [2,8,9]. When SIRPa is phosphorylated, it activates Src homology 2 domain–containing protein tyrosine phosphatase (Shp2) [11,12], which is known to be involved in central nervous system (CNS) cell survival, differentiation, and cellular morphogenesis [13,14,15]
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