Dapp1-KO 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 SH2 domain and a PH domain, and is involved in signaling processes related to cell movement, differentiation, and survival. It plays a role in immune responses, especially in leukocyte-related functions, and is also associated with the PI 3-kinase pathway [3,4].

In gene knockout (KO) mouse models, Bam32-deficient (Bam32-/-) mice showed significantly reduced WKYMVm-induced microvascular hyperpermeability and neutrophil emigration. Bam32 was crucial for WKYMVm-induced ROS production in neutrophils, and this was associated with ERK1/2 phosphorylation [1]. In another study, Bam32-/-mice had increased neutrophil chemotaxis in response to CXCL2, indicating a suppressive role of Bam32 in chemokine-induced neutrophil recruitment, which was related to Rap1 activation and PI3K-Akt signaling [2]. In addition, Dapp1-deficient mice had lower airway hyperreactivity than control mice only after diesel exhaust particle (DEP) exposure, suggesting Dapp1 as a determinant of air pollution-induced airway hyperreactivity [5].

In conclusion, Dapp1 plays essential roles in immune-related biological processes. Through KO mouse models, its functions in neutrophil-mediated microvascular hyperpermeability, chemotaxis, and air pollution-induced airway hyperreactivity have been revealed. These findings contribute to understanding the mechanisms of inflammation-related diseases and environmental-induced airway diseases [1,2,5].

References:

1. Hao, Li, Marshall, Aaron J, Liu, Lixin. 2020. Bam32/DAPP1-Dependent Neutrophil Reactive Oxygen Species in WKYMVm-Induced Microvascular Hyperpermeability. In Frontiers in immunology, 11, 1028. doi:10.3389/fimmu.2020.01028. https://pubmed.ncbi.nlm.nih.gov/32536926/

2. Hao, Li, Marshall, Aaron J, Liu, Lixin. 2021. Suppressive Role of Bam32/DAPP1 in Chemokine-Induced Neutrophil Recruitment. In International journal of molecular sciences, 22, . doi:10.3390/ijms22041825. https://pubmed.ncbi.nlm.nih.gov/33673180/

3. Anderson, K E, Lipp, P, Bootman, M, Stephens, L R, Hawkins, P T. . DAPP1 undergoes a PI 3-kinase-dependent cycle of plasma-membrane recruitment and endocytosis upon cell stimulation. In Current biology : CB, 10, 1403-12. doi:. https://pubmed.ncbi.nlm.nih.gov/11102801/

4. Dowler, S, Currie, R A, Downes, C P, Alessi, D R. . DAPP1: a dual adaptor for phosphotyrosine and 3-phosphoinositides. In The Biochemical journal, 342 ( Pt 1), 7-12. doi:. https://pubmed.ncbi.nlm.nih.gov/10432293/

5. Maazi, Hadi, Hartiala, Jaana A, Suzuki, Yuzo, Akbari, Omid, Allayee, Hooman. 2019. A GWAS approach identifies Dapp1 as a determinant of air pollution-induced airway hyperreactivity. In PLoS genetics, 15, e1008528. doi:10.1371/journal.pgen.1008528. https://pubmed.ncbi.nlm.nih.gov/31869344/