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.
Matzinger
S A
SA
Department of Pathology, Medical College of Ohio, Toledo 43699, USA.
Chen
B
B
Wang
Y
Y
Crist
K A
KA
Stoner
G D
GD
Kelloff
G J
GJ
Lubet
R A
RA
You
M
M
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D004247:DNA; D005260:Female; D005786:Gene Expression Regulation; D011905:Genes, ras; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D013045:Species Specificity; D013154:Spleen / Q000378:metabolism
D004247:DNA