Superfund Research Program

Mouse Molecular Genetics Core

Project Leader: Pamela L. Mellon
Grant Number: P42ES010337
Funding Period: 2000-2017

Project-Specific Links

Final Progress Reports

Year:   2016  2009  2004 

The Mouse Genetics Core’s major function is the creation of novel genetically manipulated mouse models for the Superfund investigators. In addition, they assist with the design, characterization, and maintenance of these important mouse models. The core is used by the laboratories of Drs. Karin, Evans, Tukey, and Taylor. A substantial array of transgenic and knock-out mouse models have been created for the Superfund projects. Highlights include the creation of transgenic mice bearing the human UGT1 locus (Tg-UGT1), p38α "floxed" mice,  p38α^F/F, used to generate mice that lack p38α expression only in hepatocytes (p38α^Δhep ), transgenic line carrying a chimeric gene consisting of the entire human CYP1A1 gene fused with a GFP reporter gene, conditional knock-outs for the IKKß gene, knock-outs of alternatively spliced exons of acetylcholinesterase, a conditional knock-out of PPARγ, total knock-outs of JNK1 and 2, and transgenic reporter systems for the detection of toxic agents. These continue to have heavy usage in the projects of the Tukey, Karin and Taylor labs.

This year, they have performed quite a number of embryonic stem cell targeting procedures, performed cryopreservation of a number of important mouse lineages for the project investigators, and created a number of lines of transgenic mice including those carrying Bacterial Artificial Chromosomes. A recent targeted knockout mouse designed to interrupt the expression of the mouse Udp-glucoronosyl transferases (ugt) locus, which encodes for ugt1A1 through 1a10, has been particularly fruitful for the Tukey lab since it serves as a model of hyperbilirubinemia and kernicterus. The longer-term goal is to model human Gilbert’s syndrome in mice. Many of these procedures are leading to creation of new mouse models that will produce important advancements and substantial progress for the projects.