Molecular Genetics Core

The main purpose of the Molecular Genetics Core is to provide a service facility that will ensure the ability of each DRC member to produce transgenic and chimeric mice from embryonic stem cells as well as transgenic rats. We will provide transgenic and knockout mice in the NOD system as our primary service. We will also provide transgenic mice in F2 (usually B6/C3H) and rats on Sprague-Dawley, and chimeric mice using the 129 strain ES cells. Embryo freezing will be provided as a means to preserve valuable, but not used, strains of mice. We will also establish an in vitro fetrilization procedure which will allow the cryopreservation of sperm in addition to embryos. In addition, the Core will develop a new immunodeficient rat model to be used as a system for studying human tissue grafts, BAC (bacterial artificial chromosomes) transgenic NOD mice to define specific diabetes susceptibility genes, and use NOD/129 F1 ES cells for NOD knockout and knockin experiments.

The goal of the Molecular Genetics Core is to provide DRC members and their collaborators with unique rodent models that are not easily duplicated by commercial facilities.

Animal Genetics Subcore

Summary

NOD mice have been carefully bred and housed in a specific pathogen free (SPF) environment to give a high incidence of diabetes. A number of transgenic and gene knockout strains on the NOD genetic background have been developed by vigorously back-crossing these strains of mice to NOD core stock. In addition, some transgenic strains have been generated by direct injection of transgene DNA into the ova of NOD mice. This subcore also maintains congenic NOD strains that serve as controls for experiments that require NOD genetic background but different MHC as well as strains that can serve as controls for the NOD MHC, which is H2g7. We offer DRC members access to an effective facility and unique animal resources so that research can be performed more efficiently and at a major cost savings. In addition, this subcore supplies NOD mice for the direct derivation of transgenic mice by injection of transgenes into the ova of NOD mice in the Animal/Transgenic Core. These mice also serve as pancreatic islet donors for investigators and islet isolations that are performed in the Islet Isolation Sub-core. Most importantly, generation of transgenic and knockout NOD mouse lines. We have developed methods of testing for NOD background genes by PCR analysis of microsatellites for the currently known NOD susceptibility loci. We have also developed a novel model of spontaneous diabetes – a “humanized” model system – HLA transgenic mouse.

Management

This subcore is directed by Li Wen, MD, PhD and provides NOD and NOD congenic mice for in vitro and in vivo experiments to DRC investigators and provides breeders to investigators. However, if a large number of mice are requested, each investigator will be asked to breed them by him/herself. Also, each investigator pays for the cost of maintenance and breeding. However, when an experiment calls for a few NOD mice on occasion, they will be provided gratis. The Core Director provides a sign-up list for DERC members to request services.

Training

The subcore provides training of breeding NOD and related mice; screening for diabetes and microsatellite marker analyses.

Director

Richard A Flavell, PhD, FRS

Sterling Professor of Immunobiology

Contact Info
Academic Office
The Anlyan Center
300 Cedar Street
New Haven, CT 06519

richard.flavell@yale.edu

Subcore Director, Animal Genetics

Li Wen, MD, PhD

Associate Professor of Medicine (Endocrinology)

Contact Info

li.wen@yale.edu