Genetic mapping of a pulmonary adenoma resistance locus (Par1) in mouse

被引:69
作者
Manenti, G
Gariboldi, M
Elango, R
Fiorino, A
DeGregorio, L
Falvella, FS
Hunter, K
Housman, D
Pierotti, MA
Dragani, TA
机构
[1] IST NAZL TUMORI, DIV EXPTL ONCOL A, I-20133 MILAN, ITALY
[2] MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA
关键词
D O I
10.1038/ng0496-455
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Lung cancer, a major cause of death in the Western world, has a poor prognosis. So far, therapeutic strategies have had only a limited effect. Lung cancer risk is strongly associated with cigarette smoking and lung cancer pedigrees are rare. However, a possible polygenic nature of inherited predisposition to this cancer has been envisaged. Mouse inbred strains with inherited predisposition and resistance to lung cancer provide an important tool for the dissection of the genetics of this complex disease. The A/J strain carries the pulmonary adenoma susceptibility 1 (Pas1) locus and develops many lung tumours. We have mapped the M. spretus-derived locus that strongly resists the tung tumorigenesis in Pas1/+ mice. This locus, pulmonary adenoma resistance 1 (Par1) maps to mouse chromosome 11, near the Rara locus, with a lod score of 5.3. In Pas1/+ mice Par1 accounts for 23% of the phenotypic variance and 10 fold reduction in total tumour volume. These results provide evidence for a major resistance locus affecting the expression of an inherited predisposition to lung cancer.
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页码:455 / 457
页数:3
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