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.
View Article and Find Full Text PDFMice deficient in the Ung uracil-DNA glycosylase have an increased level of uracil in their genome, consistent with a major role of Ung counteracting U:A base pairs arising by misincorporation of dUMP during DNA replication. A complementary uracil-excising activity apparently acts on premutagenic U:G lesions resulting from deamination of cytosine throughout the genome. However, Ung specifically processes U:G lesions targeted to immunoglobulin variable (V) genes during somatic hypermutation and class-switch recombination.
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April 1994
Gnotobiotic mice with congenital immune deficiencies were infected with the skin pathogen Dermatophilus congolensis. Athymic (nude) mice with T cell deficiency were less susceptible than nude mice which also carried the beige mutation (beige-nude) with NK cell and granulocyte defects, as part of the murine equivalent of Chediak-Higashi syndrome. The additional presence of the x-linked immunodeficiency gene in other beige mutant mice, giving reduced B cell responsiveness, did not increase their susceptibility.
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