Gene-Targeted Mice Lacking the Trex1 (DNase III) 3′→5′ DNA Exonuclease Develop Inflammatory Myocarditis
AUTOR(ES)
Morita, Masashi
FONTE
American Society for Microbiology
RESUMO
TREX1, originally designated DNase III, was isolated as a major nuclear DNA-specific 3′→5′ exonuclease that is widely distributed in both proliferating and nonproliferating mammalian tissues. The cognate cDNA shows homology to the editing subunit of the Escherichia coli replicative DNA polymerase III holoenzyme and encodes an exonuclease which was able to serve a DNA-editing function in vitro, promoting rejoining of a 3′ mismatched residue in a reconstituted DNA base excision repair system. Here we report the generation of gene-targeted Trex1−/− mice. The null mice are viable and do not show the increase in spontaneous mutation frequency or cancer incidence that would be predicted if Trex1 served an obligatory role of editing mismatched 3′ termini generated during DNA repair or DNA replication in vivo. Unexpectedly, Trex1−/− mice exhibit a dramatically reduced survival and develop inflammatory myocarditis leading to progressive, often dilated, cardiomyopathy and circulatory failure.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=444847Documentos Relacionados
- Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1
- Characterization of the human and mouse WRN 3′→5′ exonuclease
- Altered Skeletal Muscle Phenotypes in Calcineurin Aα and Aβ Gene-Targeted Mice
- Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies
- Expression of a β-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice