Abstract
We studied the effect of this mutation on UVB-induced mutagenesis in mouse skin, using a transgenic mouse harboring -phage shuttle vector-based bacterial lacZ genes as a mutational reporter. UVB increased the lacZ mutant frequency in the epidermis moderately but significantly higher in the homozygous mutant frequencies were not different appreciably among them. Ninety-eight lacZ mutant sequences isolated from the UVB-exposed epidermis of the Xpgex15-homozygous mice were analyzed and compared with mutant sequences from the wild-type mice. The spectra of the mutations were not significantly different and highly UV-specific: a high frequency of C->T transitions at dipyrimidine sites and several CC->TT tandem mutations, although the UV-specific mutations occurred more frequently at CpG sites in the mutant mice. The distreibution of the mutations observed in the lacZ transgene and the preferred sequence context of the UV-specific C->T mutations (5-TC-3> 5-CC-3>5-CT-3) in the Xpg mutant were similar to those found in the wild-type mice. Despite those similarities, we detected a previously unrecognized type of the UV-induced mutation only in the Xpg mutant, which is characterized by multiple base substitutions or frameshifts within a three-nucleotide sequence containing a dipyrimidine. The possible significance of this putative new class of mutation, which we defined as the triplet mutation, was discussed.
