Tissue-specific expression of the K-ras allele from the A/J parent in (A/J x TSG-p53) F1 mice.

Tissue-specific expression of parental K-ras allele(s) was investigated by single-strand conformation polymorphism analysis of the 3' untranslated region of the K-ras gene in normal lung, spleen, liver and kidney from (A/J x TSG-p53) F1 mice. The expression of A/J K-ras allele was equal to that of C57BL/6J allele in normal spleen, liver and kidney. However, transcripts from A/J K-ras allele were found to be 2-12-times greater than those from C57BL/6J allele in lung tissues harvested over a 20-week period. Similar to our previous observation with dimethylnitrosamine- and benzo[a] pyrene-induced lung tumors, K-ras mRNA transcribed from A/J allele was 10-40-times more abundant than those from C57BL/6J allele in all of 40 (A/J x TSG-p53) F1 mouse lung tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. In addition, K-ras mutations (G to A transitions at the second base of codon 12) were detected in 38 of 40 (95%) lung tumors and all of the mutations were found on the allele inherited from the A/J parent. These data demonstrate tissue-specific allele-specific transcription of the K-ras gene and provide further support to the thesis that K-ras allele itself is a primary mouse lung tumor susceptibility gene.