Generation of a myeloid specific Bruton’s tyrosine kinase (BTK) knockout mouse to study the role of BTK in cardiovascular disease.

Bruton's tyrosine kinase is well known for its role in B-cells biology and being a key pharmacological target in the treatment of leukemic cancers. However, BTK is also highly expressed in cells of myeloid lineage, including monocytes and macrophages, which have a fundamental role in the initiation, and critically in the successful resolution, of inflammation in cardiovascular disease. Currently, the only methods to study the role of BTK in atherosclerosis and myocardial infarction are pharmacological tools or XID mice. Both have limitations, all the tool compounds available for in vivo use have off target effects, while XID mice have a non-signalling BTK in all BTK expressing cells, Therefore, to assess the role of myeloid expressed BTK in atherosclerosis we will generate a new mouse line, that specifically targets BTK in myeloid cells, namely monocytes and macrophages, using the LysM Cre mouse crossed with a BTK^fl/fl mouse.