ABCA1 Gene Editing

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ABCA1 Gene Editing    

ABCA1 (ATP-binding cassette transporter ABCA1), also known as cholesterol efflux regulatory protein (CERP), is a membrane protein of 2261 amino acids. ABCA1 consists of two transmembrane domains of six alpha-helices and two intracellular nucleotide-binding domains, with two peptide motifs called Walker A and Walker B, which are present in many ATP-utilizing proteins.

Table 1: Characteristics and physiological roles of ABCA1

Transporter Chromosomal localization Protein weight Cellular localization Physiological functions
ABCA19q31.1254 kDaEndoplasmic reticulumCholesterol efflux
Golgi apparatusPhospholipid efflux
Plasma membrane 
  • Regulation of ABCA1

ABCA1 is regulated by post-translational protein modifications and protein-protein interactions. The interaction of apoA-I with ABCA1 prevents phosphorylation of the PEST sequence in the cytoplasmic domain of ABCA1, thereby reducing the degradation of calpain proteolysis and increasing the surface expression of ABCA1. In addition, palmitoylation regulates the localization of ABCA1 in the plasma membrane and regulates its ability to efflux cholesterol.

  • The physiological function of ABCA1
    • ABCA1 plays a crucial role in transcellular cholesterol transport and HDL synthesis in the liver and small intestine. ABCA1 also acts as a transporter of cholesterol and lipids in vascular wall cells such as endothelial cells and macrophages, as well as various other tissues including the brain.
    •  Model of ABCA1-mediated lipid efflux from cellsFigure 1: Model of ABCA1-mediated lipid efflux from cells (Boadu, E. 2005).

    • The interaction between members of the apolipoprotein family and ABCA1 activates a variety of signaling pathways, including the JAK-STAT, PKA and PKC pathways.
    • It has been reported that the expression of ABCA1 induces resistance to the anti-inflammatory diaryl heptane antioxidant curcumin.
  • ABCA1 and disease

Defects in ABCA1 may affect both serum HDL levels and overall cholesterol homeostasis. The ABCA1 mutations described so far may affect protein maturation, plasma membrane remodeling (lipase) activity, apoA-I binding, ATP hydrolysis activity or decreased cell surface apoA-I expansion activity levels.

Tangier disease caused by the deficiency of functional ABCA1 protein is a rare autosomal recessive disease. Currently, approximately 20 different mutations in the ABCA1 gene have been described, resulting in tangier disease-like phenotypes.

In addition, down-regulation of ABCA1 in senescent macrophages disrupts the ability of cells to remove cholesterol from the cytoplasm, leading to cells promoting pathological atherosclerosis (vascular thickening/hardening).

ABCA1 Gene Editing Service

CRISPR/Cas9 PlatformCB provides you with comprehensive CRISPR/Cas9 gene editing services and products to a wide range of genomics researchers. As a leading biotechnology company specializing in gene editing, we can help you effectively regulate your target genes editing (including deletion, insertion or point mutation, etc.) in vivo and in vitro using the CRISPR/Cas9 system.

  • ABCA1 Gene Editing Cell Line Generation

Our scientists have extensive experience in incorporating CRISPR/Cas9 technology into >200 different cell lines including easy-to-transfect cell lines and hard-to-transfect cells. To support your research, we provide you with end-to-end ABCA1 gene editing service from strategy design to final stable cells.

Our ABCA1 gene editing cell line generation services include

➢ Strategy design
➢ gRNA design and synthesis, donor DNA design and synthesis (if needed)
➢ CRISPR/Cas9 vector construction
➢ Transfection into the cell lines you’re interested
➢ Select the high expression cells and sort monoclonal cell
➢ Validate the right edited monoclonal cells by PCR and sequencing
➢ Delivery the stable cells and a final report

Cell lines we offered

➢ Blood Lineage Cells (RAW264.7, HMC1.2, K562, U937 etc.)
➢ Cancer Cell Lines (HEK293, HEK293T, Hela, MCF7, Neuro2a, HepG2, U87, etc.)
➢ Stem Cells (iPSC)
➢ Other Cell Lines (NIH3T3, MCF10, HEME, SW10 etc.)

  • ABCA1 Gene Editing Animal Model Generation

CRISPR/Cas9 PlatformCB also has successfully implemented CRISPR/Cas9 gene edited in animal models, which have been fully recognized by our clients. Tell us your needs, we offer you full-length ABCA1 CRISPR/Cas9 gene editing animal service and guarantee at least 2 founders or 3 F1 animals with shorter turnaround time and lower price.

Our ABCA1 gene editing animal model generation services include

➢ ABCA1 gene conventional knockout animals
➢ ABCA1 gene conditional knockout animals
➢ ABCA1 point mutation animals
➢ ABCA1 knockin animals

Alternative species: mouse, rat, rabbit, zebrafish, C. elegans, etc.

CRISPR/Cas9 PlatformCB has excellent quality management and quality assurance capabilities, providing the best gene editing services and products for academic research, biotechnology research, and drug discovery. We can adapt the solution to your detailed requirements from the early strategic design to the final model. We guarantee to provide our customers with excellent service. If you have any questions, please feel free to contact us.

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References

  1. Ayaori, M. & Ikewaki, K. Role of ATP-Binding Cassette Transporters A1 and G1 in Reverse Cholesterol Transport and Atherosclerosis. The HDL Handbook. 2014:103–131.
  2. Bachmeier BE. et al. Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells. Molecular Cancer. 2009; 8: 129.
  3. Boadu, E. & Francis G. A. The role of vesicular transport in ABCA1-dependent lipid efflux and its connection with NPC pathways. Journal of Molecular Medicine. 2005; 84(4):266–275.
  4. Luu W, Sharpe LJ. et al. The role of signalling in cellular cholesterol homeostasis. IUBMB Life. 2013; 65 (8): 675–84.
  5. Michela Pasello. et al. The ABC subfamily A transporters: Multifaceted players with incipient potentialities in cancer. Seminars in Cancer Biology. 2019; 10.004.
  6. Mohammad Mahdi Babashamsi. et al. ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019; 13(2): 1529-1534.
  7. Sposito, A. C. et al. Lipid trafficking in cardiovascular disease. Advances in Clinical Chemistry. 2019; 04.002.
For research use only. Not intended for any clinical use.

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