Transgenic Core

ABSTRACT The P01 Transgenic Core (PI – Bradford Lowell, BIDMC) will work with the Food Allergy P01 investigators to create genetically engineered mice as outlined in their three projects. A complete suite of services are available, including the ability to engineer transgenic, gene knockout and gene knockin mice. Two common forms of gene knockin mice include recombinase driver mice and mice bearing lox-modified alleles. For recombinase-driver mice, “marker” genes known to be neuron subtype- or cell subtype-specific, are engineered to drive expression of DNA recombinases (e.g. Cre recombinase). Once generated, such mice are used with recombinase-dependent tools to monitor, map and manipulate the unique subtypes of neurons and cells. In the case of mice bearing lox-modified alleles, functionally important genes are engineered to be flanked by lox sites. This makes it possible to selectively delete that gene from any cre-expressing neuron or cell. Of note, the CRISPR-based genetic engineering strategy being employed can be done in any mouse strain, including BALB/c which is an important strain for food allergy research. Additional services available include mouse ES cell-based gene targeting, cryopreservation of mutant mice in the form of frozen embryos or frozen sperm and resurrection of mutant mice from frozen embryos or frozen sperm. The Transgenic Core PI, Bradford Lowell, has many years of experience in the generation and utilization of genetically engineered mice to study neuronal function, including that of vagal motor neurons that innervate the gut. The BIDMC Transgenic Facility manager, Joel Lawitts, has many years of experience in culturing and manipulating preimplantation mouse embryos, and in running the BIDMC Transgenic Facility. Together, Lowell, Lawitts and the BIDMC Transgenic Facility have provided extensive mouse genetic engineering services for many years to numerous investigators from many different institutions. Indeed, from 2016 to present, 188 services (mostly CRISPR projects) have been provided to 39 different investigators from 12 different institutions. Hence, this P01 Transgenic Core has vast experience and can meet all the genetic engineering needs of the Food Allergy P01 investigators.