The NIEHS knock out core (KOC) is a servicing core facility with some research opportunity. Each project in the core is a long-term commitment from start to finish, and several projects are at different stages of completion in the core at any given time of the year. The core works very closely with the investigator since the inception of the project, which typically starts with meeting with PI's group for developing the targeting strategy and continues until the mutant mouse is made. KOC helps investigators to generate the mutant mouse customized to their research needs;including traditional knockouts, conditional knockout and knock-ins. It also provides assistance to establish and culturing the mutant cells for in vitro studies, along with dissecting the early stage embryos and help establishing the genotyping strategies.
Development of mouse models to determine the function of a gene or to identify the environmental effect on a disease process is the most effective way to move forward and identify the possible therapeutics to prevent or to slow down a disease process. The mouse models we develop in the KOC are used primarily to determine the function of a gene, the regulation of a gene, to determine the significance of a particular motif or a domain or using the mutant mouse to the environmental toxicants and determine the susceptibility of the mutant animals towards the environmental pollutants. For example, we identified abnormal glucose metabolism in heterozygous mutant mice for a type 1 BMP receptor (Alk3) and working on identifying the downstream target genes to find out the molecular mechanism of this abnormality. This information could potentially be important towards the greater good of human life and may add values for improving quality of human lives. In summary, the mutant mouse models we develop in the NIEHS KOC are potentially vital tools to improve the human health quality and to identify the target genes and the potential therapeutics to prevent serious illnesses.
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