JAK3 Gene Editing    

JAK3 is a protein coding gene. The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. Other members of the Janus family include JAK1, JAK2 and TYK2. JAKs are conserved in domain structure, with an N-terminal FERM domain and a Src homology 2 (SH2)-like domain, followed by a pseudokinase domain (JAK homology 2, JH2) and a tyrosine kinase domain (JH1). They are relatively large kinases of approximately 1150 amino acids with apparent molecular weights of 120-130 kDa. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Non-receptor tyrosine kinase is also involved in various processes, such as cell growth, development, or differentiation.

JAK3 mediates essential signaling events in both innate and adaptive immunity, and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, it plays a pivotal role in signal transduction via its sole association with type I receptors sharing the common subunit gamma (γc), such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R, which regulate development and activation of lymphoid lineage cells. In IL-2 receptor (IL-2R) signaling, as well as cytokine signaling, when ligand binds to extracellular domain of cell surface receptors β or γ chains, JAK1 and JAK3 phosphorylates specific tyrosine residues of receptor subunits on the cytoplasmic tails, creating docking sites for signal transducers and activators of transcription (STATs) proteins. Then, for example, STAT5A and STAT5B are recruited. Subsequently, JAK3 phosphorylates the STATs proteins. Phosphorylated STATs then form homodimer or heterodimers, and translocate to the nucleus to activate transcription of specific target genes in a cytokine-specific fashion.

Type	Subgroup	Cytokine Receptor	JAK Kinase
type I receptors	homodimeric	EPO, TPO, GH, G-CSF	JAK2
	uses common beta chain (CSF2RΒ)	IL-3, IL-5, GM-CSF	JAK2
	uses gp130 chain	IL-6, IL-11	JAK1, JAK2, Tyk2
	uses common gamma chain (γc)	IL-2, IL-4, IL-7, IL-9, IL-15, IL-21	JAK1, JAK3
type II receptors		IFN-α, IFN-β, IFN-γ	JAK1, JAK2, Tyk2

Table 1 Some cytokine receptors and their involvement with JAK kinases （O'Shea JJ et. al, 2005)

Mutations in JAK3 gene are associated with autosomal SCID (severe combined immunodeficiency disease). JAK3 mutations are also found in patients of T-cell acute lymphoblastic leukemia (T-ALL), acute megakaryoblastic leukemia, T-cell prolymphocytic leukemia, and juvenile myelomonocytic leukemia and natural killer T-cell lymphoma (NK/T-lymphoma). JAK plays a central role in the control of lymphopoiesis. The pseudokinase domain (JAK homology 2, JH2) of JAK3 shows significant sequence homology with classical protein kinases but several conserved functional residues or motifs are missing or altered. JAK JH2s is of particular interest as approximately half of clinical JAK3 mutations cluster into it. Recent studies have focused on tyrosine kinases as potential targets for the treatment of Rheumatoid arthritis (RA), which is a chronic, systemic disease characterized by persistent inflammatory synovitis. Among them, inhibitors specific for the JAK family are, so far, the most efficacious in treating RA. Selective JAK3 inhibition should be sufficient for immunosuppression without causing effects outside the immune system.

JAK3 Inhibition Mechanism (Warren J Leonard et al., 2016)

Genome Editing is revolutionizing biomedical research, due to its high efficiency, ease-of-use, and relatively low cost. CRISPR/Cas9 Platform^CB, a global biotechnological company specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene editing products and services for academic research, biotech research and pharmaceutical drug discovery. With products for CRISPR-Cas9 clones, validation and screening kits, pre-made transfected stable cell lines, and more for precision genome editing, our complete solutions for genome editing provide you with a wealth of tools to help you every step of the way in your genome editing workflow.

• Gene Editing Cell Line Generation

Our specialists will provide with helpful tips on designing and using gRNA and Cas9 constructs, CRISPR libraries, designing KO mammalian cell lines, and more!

Service	Details	Cell Line Options *
Knockout Cell Line Service	Single gene knockout cell line	Available for any transfection-suitable cell lines, including A549, CHO-K1, HEK293, HEK293T, HCT116, MCF7, MDCK, U937, RPMI 8866, HT-29, MDA-MB-231, 4T1, A20, etc.
	Transfection-based
	Customer specifies gene/locus region and cell line of interest*
Customized Knockout Cell Line Service	Single or multiplex genes editing knockout cell line	Any cancer cell line
	Transfection/Lentivirus/Ribonucleoprotein-based
	Customer specifies gene/locus region and cell line of interest*

* It is preferred that customers provide their own cell lines, despite available cell lines can be purchased by Creative Biogene for an additional fee.

Related Details

Guide RNA Design:

Our expert scientists from Creative Biogene will optimize your guide RNA sequence for maximized efficiency and minimal off-target effects using best design algorithms.

Materials Needed from Clients:

Target gene name.

Target gene sequence, if the whole genome sequence is unavailable.

Quality Control

Sequence Chromatogram

Quality Assurance Certificate

Quantitative RT-PCR Validation (Optional)

Western Blot Validation (Optional)

Deliverables

Knockout cell lines validated by sequencing

Delivery Time

Starting from 4 weeks

• Gene Editing Animal Model Generation

Service	Details	Delivery Time	Options *
Gene Knockout Mouse Generation	Conditional Knockout Mouse Conventional Knockout Mouse Point Mutation Mouse	Starting from 4 weeks
Gene Knockin Mouse Generation	CRISPR/Cas9 Knockin Mouse Rosa26 Knockin Mouse	Starting from 4 weeks	Any other target gene knockin mouse generation
Custom Animal Models	Custom Rat Model Custom Rabbit Model Custom Zebrafish Modell Custom C. elegans Model Custom Drosophila Model	Starting from 4 weeks	Any other animal models according to our client's requirements

CRISPR/Cas9 Platform^CB is devoted to providing the best gene editing services to accelerate the achievement of your research goals. We are committed to providing the most reliable and effective research services and products with excellent quality management and quality assurance capacity. If you have any questions, please feel free to contact us.

Related Products at CRISPR/Cas9 Platform^CB

CATALOG NO.	PRODUCT NAME	PRODUCT TYPE	INQUIRY
CCKM0298	B6J-Jak3em1Cd	knockout mouse	Inquiry
CDKM-0468	B6J-Jak3em1Cflox	knockout mouse	Inquiry

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