Dapp1-flox Mouse

Dapp1, also known as Bam32 (B cell adaptor molecule of 32 kDa), is a dual adaptor protein for phosphotyrosine and 3-phosphoinositides. It contains an amino-terminal Src homology 2 (SH2) domain and a carboxy-terminal pleckstrin homology (PH) domain. Dapp1 functions downstream of phosphoinositide 3-kinase enzymes, playing a role in multiple signaling pathways related to immune cell activation and function [4,8]. It is involved in lymphocyte proliferation, recruitment during inflammation, and endosomal trafficking [1,3,6,7,8]. Gene knockout (KO) mouse models have been crucial in studying Dapp1's functions.

In Bam32-deficient (Bam32-/-) mice, WKYMVm-induced microvascular hyperpermeability and neutrophil emigration were significantly reduced, suggesting that Dapp1-dependent, ERK1/2-involving ROS generation in neutrophils is critical in this process [1]. In chemokine-induced neutrophil recruitment, Bam32-/-mice showed increased neutrophil chemotaxis, indicating that Dapp1 has a suppressive role in this process by regulating Rap1 activation [2]. In B-cell-related studies, Bam32-deficient mice had normal germinal center (GC) initiation but premature GC dissolution, along with impaired Ab affinity maturation, suggesting Dapp1 is required for GC progression [7]. Bam32-deficient B cells also had reduced ability to form polarized conjugates with T cells and activate Ag-specific T cells, showing its role in B-cell adhesion and Ag presentation [6]. In addition, Dapp1-deficient mice exhibited significantly lower airway hyperreactivity than control mice only after diesel exhaust particle exposure, validating Dapp1 as a determinant of air-pollution-induced airway hyperreactivity [5].

In conclusion, Dapp1 plays essential roles in immune-related processes such as neutrophil-mediated inflammation, B-cell activation and function, and the response to air-pollution-induced airway hyperreactivity. The use of Dapp1 KO mouse models has revealed its functions in these specific disease-relevant biological processes, contributing to our understanding of the underlying mechanisms in inflammation, immune responses, and environmental-factor-related diseases.