Genetic mapping of a putative tumor suppressor locus that influences tumorigenesis and metastasis in mice.
The tumor suppressor TP53 is mutated in approximately 70% of Li-Fraumeni syndrome (LFS) families; however, other genes may lead to the predisposition to tumors in other families. We developed a mouse model to search for other tumor suppressors that may be involved in the syndrome. Inbred CE/J mice, which succumb to multiple types of tumors similar to those found in LFS, were crossed with the Trp53-null 129-Trp53tm1Tyj mouse. We monitored the tumor onset and type and found a significant earlier tumor onset in the CE/J:129-Trp53tm1Tyj mice compared with 129-Trp53tm1Tyj mice with a Trp53-null allele. Additionally, in CE/J:129-Trp53tm1Tyj-Trp53+/- mice, the tumors metastasize, which does not occur in other strains of mice. Using simple-sequence length polymorphism analysis for loss of heterozygosity in tumors, we identified a putative tumor suppressor locus within 1 cM on mouse chromosome 11, which encompasses 12 mapped genes.
Department of Chemistry and Biochemistry, Ohio University, Athens 45701, USA.
Bernard
B
Ayanga
Roger
R
Price
Xiangjun
X
Gu
Guillermina
G
Lozano
Susan C
SC
Evans
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D016147:Genes, Tumor Suppressor; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009362:Neoplasm Metastasis / Q000235:genetics*; D011110:Polymorphism, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53