Lead Inventors:
Jeanine D'Armiento MD Ph.D., Asahiro Morishita,
Steven Greenberg Ph.D.
Macrophage function studied using mouse strain with genes that can be switched on or off :
The use of knock-out mouse models (where certain genes are deleted) is a critical research tool in understanding gene function. A knock-out animal is created at the embryonic stage of development and global in scope. Not all genes can be effectively studied this way due to severe developmental impairment or even lethality of the knock-out. Thus, there is a need for a more sophisticated knock-out scheme, where tissue targeting is more specific and the knock-out state is switchable.
Transgenic mouse model where gene knockout is switchable and tissue specific for macrophages:
The technology is a transgenic mouse model where the gene knockout is switchable and tissue specific for macrophages, immune cell which digests foreign pathogens and stimulates other immune processes. Macrophages have been identified as a critical component in many chronic inflammatory diseases. The technology makes the knock-out state activatable by exposure to physiologically achievable levels of an activator molecule, tamoxifen. Not only can genes be selectively knocked out, but also gene activation can be performed as well using the same technology. In addition to being switchable the knock-out is limited to the targeted tissue, in this case macrophages, and thus gene function is not interrupted in monocytes and other progenitor bone marrow cells when the knock-out condition is induced. This controllable and tissue specific functionality has been demonstrated experimentally.
Applications:
• A research tool for inducible gene knock-out as well as gene activation of known gene sequences in macrophages to better study their role in inflammatory disease
• A platform to additionally probe the role of genes, previously inaccessible to conventional knock-out methods, in macrophage function
• Application of the same scheme to other highly differentiated and specialized tissues where conventional knock-out is undesirable or impossible
Advantages:
• The knockout state is inducible allowing normal gene function until such time as the knockout is desired, enabling previously impossible knock-out studies
• The knockout is tissue specific for macrophages and does not effect monocytes or other bone marrow progenitors to the macrophage thus avoiding convoluting effects on animal physiology and immune function
Patent Status: Copyright / Animals available for fee
Licensing Status: Available for licensing