Bruton’s tyrosine kinase (Btk) is a cytoplasmic enzyme encoded by the human BTK gene that plays a crucial role in B cell development, survival, proliferation and differentiation. Btk defect leads to X-linked agammaglobulinemia (XLA), a rare genetic disorder that strongly reduces the immune system, thereby affecting the ability of the organism to fight effectively against infections. Btk is also an important target for the development of innovative therapies (i.e., Btk inhibitors) for patients suffering hematologic malignancies such as chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL).

Applications

As rats more accurately reflect human physiology than mice, genOway has developed the first preclinical Btk Knockout rat model (Btk KO) to help scientists study a broad spectrum of medical fields, including:

• Immunology
• B cell malignancies (e.g., diffuse large B-cell lymphoma, chronic lymphocytic leukemia)
• Autoimmune diseases with aberrant B cell responses (e.g., rheumatoid arthritis, systemic lupus erythematosus)
• Hematology (e.g., hemostasis, thrombosis)
• Toxicology
• Screening of novel Btk inhibitors for treatment of several hematologic cancers and autoimmune diseases
• Oncology (e.g., pancreatic cancer, breast cancer)

Model features

• Lack of Btk protein expression
• B-cell developmental defects (i.e., decreased number of peripheral B cells, defects in B-cell maturation and activation)
• Sprague Dawley outbred genetic background