Abstract
Inherited predisposition to lung cancer is a phenotypic trait shared by different mouse inbred strains that show either a high or an intermediate predisposition. Other strains are instead genetically resistant. The Pasl locus is the major determinant of lung cancer predisposition in the A/J strain (Gariboldi et al. 1993). To define the determinants of susceptibility to lung tumorigenesis in the highly susceptible SWR/J and in the intermediately susceptible BALB/c mice, we analyzed (BALB/c x SWR/J)F2 and (BALB/c x C3H/He)F2 crosses by genetic linkage experiments. The present results provide unequivocal evidence that the same Pas1/+ allele that leads to lung cancer predisposition is shared by A/J, SWR/J, and BALB/c strains. The intermediate susceptibility of the BALB/c strain would result by interaction of Pas1 locus with lung cancer resistance loci.
Similar content being viewed by others
References
Atchley WR, Fitch WM (1991) Gene trees and the origins of inbred strains of mice. Science 254, 554–558
Chen B, Johanson L, Wiest JS, Anderson MW, You M (1994) The second intron of the K-ras gene contains regulatory elements associated with mouse lung tumor susceptibility. Proc Natl Acad Sci USA 91, 1589–1593
Conover WJ, Iman RL (1981) Rank transformations as a bridge between parametric and nonparametric statistics. Am Statistician 35, 124–129
Devereux TR, Wiseman RW, Kaplan N, Garren S, Foley JF, White CM, Anna C, Watson MA, Patel A, Jarchow S, Maronpot RR, Anderson MW (1994) Assignment of a locus for mouse lung tumor susceptibility to proximal chromosome 19. Mamm Genome 5, 749–755
Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, Husain Z, Dredge R, Daly MJ, Ingalls KA, O’Connor TJ, et al. (1996) A comprehensive genetic map of the mouse genome. Nature 380, 149–152
Dragani TA, Manenti G, Delia Porta G (1991) Quantitative analysis of genetic susceptibility to liver and lung carcinogenesis in mice. Cancer Res 51, 6299–6303
Dragani TA, Manenti G, Pierotti MA (1995) Genetics of murine lung tumors. Adv Cancer Res 67, 83–112
Festing MFW, Yang A, Malkinson AM (1994) At least four genes and sex are associated with susceptibility to urethane-induced pulmonary adenomas in mice. Genet Res 64, 99–106
Gariboldi M, Manenti G, Canzian F, Falvella FS, Radice MT, Pierotti MA, Delia Porta G, Binelli G, Dragani TA (1993) A major susceptibility locus to murine lung carcinogenesis maps on chromosome 6. Nature Genet 3, 132–136
Lander ES, Green P, Abrahamson J, Barlow A, Daly MJ, Lincoln SE, Newburg L (1987) MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1, 174–181
Lincoln SE, Daly M, Lander ES (1992a) Constructing genetic maps with MAPMAKER/EXP. 3.0. Whitehead Institute Technical Report
Lincoln SE, Daly M, Lander ES (1992b) Mapping genes controlling quan- titative traits with MAPMAKER/QTL 1.1. Whitehead Institute Technical Report
Malkinson AM, You M (1994) The intronic structure of cancer-related genes regulates susceptibility to cancer. Mol Carcinog 10, 61–65
Manenti G, Binelli G, Gariboldi M, Canzian F, De Gregorio L, Falvella FS, Dragani TA, Pierotti MA (1994) Multiple loci affect genetic predisposition to hepatocarcinogenesis in mice. Genomics 23, 118–124
Manenti G, Falvella FS, Gariboldi M, Dragani TA, Pierotti MA (1995) Different susceptibility to lung tumorigenesis in mice with an identical Kras2 intron 2. Genomics 29, 438–444
Obata M, Nishimori H, Ogawa K, Lee GH (1996) Identification of the Par2 (Pulmonary adenoma resistance) locus on mouse Chromosome 18, a major genetic determinant for lung carcinogen resistance in BALB/ cByJ mice. Oncogene 13, 1599–1604
Paterson A, Lander ES, Lincoln SE, Hewitt J, Peterson S, Tanksley S (1988) Resolution of quantitative traits into Mendelian factors using a complete RFLP linkage map. Nature 335, 721–726
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Manenti, G., Gariboldi, M., Fiorino, A. et al. Pas1 is a common lung cancer susceptibility locus in three mouse strains. Mammalian Genome 8, 801–804 (1997). https://doi.org/10.1007/s003359900582
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s003359900582