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Updated: Sep 27, 2026
Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
Published on: April 3, 2011
Mapping of genetic modifiers of thymic lymphoma development in p53-knockout mice
Yukie Ochiai1, Yasushi Tamura, Yuko Saito
1Department of Gene Regulation, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi-doori 1-757, Niigata 951-8122, Japan.
Abstract:
The strain dependency of the spectrum and latency of tumors has been reported in p53-deficient (KO) mice, suggesting the presence of modifiers for the outcome of the p53 deficiency. The modifiers provide clues to the oncogenic pathway in cells lacking p53, the most frequently mutated gene in a wide variety of human cancers. To search the modifiers, we induced 160 lymphomas and 69 skin tumors by gamma-irradiation of p53(KO/+) backcross mice between BALB/c and MSM strains and performed genome scan. BALB/c-derived alleles at three loci on chromosome 19, Mp53D1 (modifier of p53-deficiency) at D19Mit5, Mp53D2 at D19Mit90 and Mp53D3 at D19Mit123, extended the latency of thymic lymphoma development (P values in Mantel-Cox test were 0.0007, 0.0007 and 0.0003, respectively). Mp53D3 also increased the latency of skin tumors (P value, 0.0008). The linkage of Mp53D2 was confirmed by the experiment using 94 p53-KO mice consomic for chromosome 19, providing a significant linkage. However, the linkage was not confirmed for Mp53D1 or Mp53D3, suggesting epistasis of genes involved in the tumorigenesis.
Insights
Genetic modifiers influence tumor development in p53-deficient mice. Researchers identified specific genetic loci on chromosome 19 that extend tumor latency, offering insights into cancer pathways.
Area of Science:
- Genetics
- Oncology
- Cancer Research
Background:
- Tumorigenesis in p53-deficient mice shows strain dependency, indicating modifier genes.
- Understanding these modifiers is crucial for deciphering oncogenic pathways in cancers with p53 mutations.
Purpose of the Study:
- To identify genetic modifiers influencing tumor latency and spectrum in p53-deficient mice.
- To investigate the role of specific genetic loci in cancer development.
Main Methods:
- Genome-wide scan was performed on 160 lymphomas and 69 skin tumors induced by gamma-irradiation in p53-deficient mice.
- BALB/c and MSM mouse strains were used in backcross experiments.
- Linkage analysis and consomic mouse experiments were conducted to confirm genetic loci.
Main Results:
- Three loci on chromosome 19 (Mp53D1, Mp53D2, Mp53D3) were associated with extended thymic lymphoma latency.
- Mp53D3 also increased skin tumor latency.
- Linkage for Mp53D2 was confirmed using consomic mice, while Mp53D1 and Mp53D3 showed potential epistasis.
Conclusions:
- Specific genetic loci on chromosome 19 act as modifiers of p53 deficiency in tumorigenesis.
- Mp53D2 is a confirmed modifier, while Mp53D1 and Mp53D3 may be influenced by epistatic interactions.
- These findings provide insights into cancer development pathways and potential therapeutic targets.
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