Transgenic and Genome Engineering Core Facility
The development of the techniques for introducing foreign DNA into the germ line of mice by microinjection and those of engineering embryonic stem cells prior to injection to mouse blastocyte had yielded two powerful experimental tools: the ability to overexpress or suppress genes in specific tissues of a mouse (transgenic mice), and the power to ablate specific gene expression in the whole mouse or in a tissue specific manner (knock out mice). Since the establishment of these technologies, their use has allowed exploring the role of a variety of genes during development, as well as the importance of these genes for certain physiological and biochemical processes and for the development of disease. Although the gene knock out technology is developed for a mouse model, several transgenic animals (including rats, pigs, etc.) have been studied and reported. The mouse core facility at Boston University School of Medicine provides centralized, expert service to produce successfully these animal models for investigators at Boston University and as an outside service. Thus far, this core has produced animal models relevant to cancer biology, as well as to hematopoietic, cardiovascular, pulmonary, gastric and immunological diseases.
Examples of mouse models generated at our core facility
Figure 1Figure 2Figure 1: The tGO transgene is a fusion protein made up of the cytoplasmic and TM domains of the transferring receptor and the immunogenic peptides of ovalbumin linked to a tetracycline regulated promoter. The tGO mice can be bred to transgenic lines in which transactivator expression is regulated by an assortment of tissue specific promoters to establish model systems for the analysis of autoimmune disease. These investigations were led by Dr. Ann Rothstein, who indicated: “the studies were greatly facilitated by the ability of the Transgenic Core to inject the tGO construct directly into BALB/c oocytes.” For more details see What is New in Our FacilityFigure 2: T his figure is from Yang et al. JCI 2006 116:1913, which represents collaborative efforts of investigators at BUSM (Dr. Ravid, senior investigator). This study describes the generation of the first A2b adenosine receptor knock out mouse model. It also includes the ?-gal gene knocked-in instdead of the deleted receptor. This model was crucial in revealing the role of this receptor in vascular function and tissue regeneration. Shown are ?-Gal expression patterns in different vascular tissues.