C57BL/6JCya-Dapp1em1flox/Cya
Common Name:
Dapp1-flox
Product ID:
S-CKO-09543
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Dapp1-flox
Strain ID
CKOCMP-26377-Dapp1-B6J-VA
Gene Name
Product ID
S-CKO-09543
Gene Alias
Bam32
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
3
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Dapp1em1flox/Cya mice (Catalog S-CKO-09543) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000029806
NCBI RefSeq
NM_011932
Target Region
Exon 3
Size of Effective Region
~0.6 kb
Detailed Document
Overview of Gene Research
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.
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/
6. Al-Alwan, Monther, Hou, Sen, Zhang, Ting-ting, Makondo, Kennedy, Marshall, Aaron J. 2010. Bam32/DAPP1 promotes B cell adhesion and formation of polarized conjugates with T cells. In Journal of immunology (Baltimore, Md. : 1950), 184, 6961-9. doi:10.4049/jimmunol.0904176. https://pubmed.ncbi.nlm.nih.gov/20495066/
7. Zhang, Ting-ting, Al-Alwan, Monther, Marshall, Aaron J. 2009. The pleckstrin homology domain adaptor protein Bam32/DAPP1 is required for germinal center progression. In Journal of immunology (Baltimore, Md. : 1950), 184, 164-72. doi:10.4049/jimmunol.0902505. https://pubmed.ncbi.nlm.nih.gov/19949096/
8. Marshall, A J, Zhang, T, Al-Alwan, M. . Regulation of B-lymphocyte activation by the PH domain adaptor protein Bam32/DAPP1. In Biochemical Society transactions, 35, 181-2. doi:. https://pubmed.ncbi.nlm.nih.gov/17371232/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen