The core provides multiple services that fall into four categories: microinjection, gene targeting, genetic analysis and assisted reproduction. The major services are outlined below.
The transgenic mouse has assumed increasing importance as an experimental system in recent years. Studies of normal gene function, altered gene expression, cis elements responsible for tissue-specific patterns of gene expression, and the production of animal models for human diseases are but some of the types of studies made possible by transgenic mouse technology. The core provides a centralized service to efficiently produce transgenic mice for basic research for University of Virginia researchers and affiliated faculty.Our facility is located within a microbiologic barrier in the MR5 vivarium, so that mice supplied to you are as “clean” as those purchased from approved vendors, e.g. JAX.
We microinject your DNA construct into the male pronucleus of the mouse zygote, and reimplant these into foster mothers to make transgenic mice. From one to several hundred copies of the transgene are integrated, usually at a single site and arranged in head to tail tandem arrays. Each transgenic founder animal will have the transgene integrated at a unique genomic site that may affect the expression of the transgene. We have made hundreds of transgenic lines from many different constructs. We provide a guarantee of 3 founder animals per construct.
The core can begin a new gene targeting project by consulting with investigators in the design of the targeting construct. We outsource the construct making process.
We perform gene targeting in ES cells of your choice and provide you with selection drug resistant ES cell clones for Southern screening.
We microinject your targeted embryonic stem (ES) cells into the blastocoel of the 3.5 day mouse embryo and implant these into foster mothers to make chimeric mice. This is a crucial step in the production of mice carrying a targeted mutation. We have been very successful at producing chimeric mice giving high rates of germline transmission of targeted ES cells carrying the desired mutation.