Genetically engineered mice yield clues to 'knocking o...(ion that affects more than 40 million pe...)

In collaboration with Dr. Lloyd's group, a second research team under George W. Teebor at NYUSM engineered mice that were missing either the neil1 or the nth1 gene (nth1 encodes for another DNA glycosylase, the NTH1 protein) or both these genes. These latter are known as neil1/nth1 double knockouts. NIST's Dizdaroglu and guest researchers Pawel Jaruga and Gldal Kirkali found that both types of knockout mice exhibited significant accumulation of two lesions called formamidopyrimidines in the DNA of the liver, kidney and brain. This indicates that there was a lack of DNA repair in these organs.

During the second year of life, both types of mice also developed pulmonary and hepatocellular (liver cell) tumors. Double knockout mice had a higher incidence of tumors than the single knockouts.

The researchers state that their results emphasize the role of DNA repair in preventing carcinogenesis. The work may lead to the development of new measurement methods and reference materials for accurate and reproducible assessments of DNA damage and repair and contribute to understanding the role of oxidatively induced DNA damage and its repair in carcinogenesis. Future studies will focus on the role of NEIL1 in disease processes.

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