hBTK Mouse

The Bruton's Tyrosine Kinase (BTK) is a non-receptor cytoplasmic tyrosine kinase encoded by the BTK gene, which is primarily expressed in hematopoietic tissues including B cells, mast cells, macrophages, and platelets, and produces multiple protein isoforms via alternative splicing. Its crucial function is to serve as a key component of the B-cell receptor (BCR) signaling pathway, promoting essential B-cell development, proliferation, differentiation, and survival, as well as playing roles in innate immunity signaling via Toll-like receptors (TLRs) and Fc receptors, and in osteoclast and platelet function ^[1]. Mutations in the BTK gene cause the primary immunodeficiency X-linked agammaglobulinemia (XLA), characterized by the failure to produce mature B lymphocytes, while its overactivation and overexpression are implicated in a range of associated diseases, most notably B-cell malignancies such as Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), as well as autoimmune conditions like Sjogren's syndrome and Multiple Sclerosis (MS), making BTK a major therapeutic target for small-molecule inhibitors ^[2]. BTK inhibitors may also find a role in severe allergic disease, such as food allergy ^[3].

hBTK mouse is a humanized model generated using gene editing technology, in which the coding sequence of exon 2 to partial intron 4 was replaced with Kozak-Human BTK CDS-3’UTR of Mouse Btk-WPRE-BGH pA cassette. This model can be used to study the pathological mechanisms and therapeutic approaches of B-cell malignancies, autoimmune conditions, and severe allergic disease, as well as for the development of BTK-targeted drugs.