Abstract
Cynomolgus macaques (Macaca fascicularis) are an established animal model of asthma, which exhibit different responses to allergen exposure that are clinically relevant. The chemokine ligand gene (CCL7) encodes Monocyte Chemotactic Protein-3, which has an important role in asthma pathogenesis. While CCL7 polymorphism in humans is associated with asthma phenotype, very little is known about CCL7 in nonhuman primate models of respiratory disease. The objective of this study was to isolate and characterize CCL7 gene in cynomolgus macaques of Indonesian origin. In this study, we used sequencing and bioinformatics technique for gene isolation, characterization, and protein 3D structure prediction. We isolated a 2253 base-pair (bp) sequence of CCL7 in cynomolgus macaques, which exhibited 95% similarity in coding sequence to human CCL7. The amino acid sequence was more closely clustered with human CCL7 than with that of rodents. Importantly, the predictive protein structure of CCL7 was similar to that in humans. These similarities in CCL7 suggests the potential of cynomolgus macaque as a translational model to study asthma, particularly in the context of genetics and role of chemokines such as CCL7.
Highlights
Asthma is a chronic disease characterized by inflammation, obstruction, and remodelling of the airways coupled with breathlessness and wheezing (Zafari et al 2018)
The chemokine ligand gene (CCL7) encodes Monocyte Chemotactic Protein-3, which has an important role in asthma pathogenesis
While C Motif Chemokine Ligand 7 (CCL7) polymorphism in humans is associated with asthma phenotype, very little is known about CCL7 in nonhuman primate models of respiratory disease
Summary
Asthma is a chronic disease characterized by inflammation, obstruction, and remodelling of the airways coupled with breathlessness and wheezing (Zafari et al 2018). Asthma is a worldwide health problem and researchers continuously study genetic factors affecting its pathogenesis and intervention strategies. Little is known concerning the association of genetic factors with asthma profile in the NHP model. C-C Motif Chemokine Ligand plays a key role in asthma pathogenesis. The association between CCL7 polymorphism and asthma phenotype have been reported in humans (Park et al 2005; Batra et al 2011). Previous study reported that CCL7 expression was high in the airway of asthmatic NHPs (Zou et al 2002). It is unknown whether polymorphism of this gene exists in NHPs, in the cynomolgus macaque, due to limited information on CCL7 gene and protein expression in the species
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