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Genetic mapping of a putative tumor suppressor locus that influences tumorigenesis and metastasis in mice

✍ Scribed by Bernard Ayanga; Roger Price; Xiangjun Gu; Guillermina Lozano; Susan C. Evans


Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
243 KB
Volume
45
Category
Article
ISSN
1045-2257

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✦ Synopsis


Abstract

The tumor suppressor TP53 is mutated in ∼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‐__Trp53__tm1Tyj mouse. We monitored the tumor onset and type and found a significant earlier tumor onset in the CE/J:129‐__Trp53__tm1Tyj mice compared with 129‐__Trp53__tm1Tyj mice with a Trp53‐null allele. Additionally, in CE/J:129‐__Trp53__tm1Tyj‐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. © 2006 Wiley‐Liss, Inc.