The D5Mit7 locus on mouse chromosome 5 provides resistance to  -ray-induced but not N-methyl-N-nitrosourea-induced thymic lymphomas

Kodama, Yasumitsu; Yoshikai, Yoshihiro; Tamura, Yasushi; Wakana, Shigeharu; Takagi, Ritsuo; Niwa, Ohtsura; Kominami, Ryo

doi:10.1093/carcin/bgg177

Cited by 12 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For tumours following radiation exposure, mapping of susceptibility loci has been performed for lymphoma and leukaemia. [14][15][16][17] In a previous study, we found evidence for 2 discrete loci on mouse chromosome 7 and 14, which in combination confer an increase in a-particle induced OS incidence from 22 to 75%. 18 These 2 loci account for about one-fifth of the entire tumour susceptibility, with some indications for nonadditive genetic interaction.…”

mentioning

confidence: 77%

“…Mapping and identification of modifier genes that govern congenital cancer susceptibility in inbred mouse strains have been demonstrated following tumour induction by chemical carcinogens or targeted germline mutations10, 11, 12, 13. For tumours following radiation exposure, mapping of susceptibility loci has been performed for lymphoma and leukaemia 14, 15, 16, 17…”

mentioning

confidence: 99%

See 1 more Smart Citation

Multilocus inheritance determines predisposition to α‐radiation induced bone tumourigenesis in mice

Rosemann

Kuosaite

Kremer

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

In a recent study, we presented evidence for genetic predisposition governing radiation osteosarcomagenesis in mice. Following the incorporation of the bone-seeking a emitter 227 Th,~25% of the variance in osteosarcoma incidence was determined by inherited genetic factors. We have now mapped 5 susceptibility loci in crosses between the more susceptible BALB/c and the more resistant CBA/Ca strains. The major QTL on chromosome 14 overlaps with a locus that was already found in our previous study, using different strains of mice. Here, we investigate the effect by which the major susceptibility locus and 4 minor modifier loci interact to influence osteosarcoma predisposition. Following incorporation of the bone-seeking isotope, 100% of mice that harbour high-risk genotypes at all 5 susceptibility loci develop osteosarcoma with an average of 472 days latency times. In 10 mice inheriting exclusively low-risk genotypes only 1 osteosarcoma was found, arising after 733 days latency time. Inheritance of distinct combinations of BALB/c and CBA/Ca alleles at the susceptibility loci confer more extreme phenotypes in terms of susceptibility or resistance than observed in either of the two parental inbred strains. From the present study, we demonstrate that additive effects of multiple alleles, each making only a minor phenotypic contribution, can combine and significantly alter tumour risk. This mechanism can be of particular importance in genetically heterogeneous populations such as man. ' 2005 Wiley-Liss, Inc.

show abstract

mentioning

confidence: 77%

mentioning

confidence: 99%

Multilocus inheritance determines predisposition to α‐radiation induced bone tumourigenesis in mice

Rosemann

Kuosaite

Kremer

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…MSM/Ms itself is a strain resistant to thymic lymphomagenesis. However, the Thyls3 locus on chromosome 5 of MSM/Ms exceptionally conferred susceptibility to lymphomas [43]. They induced lymphomas in these congenic mice in two ways.…”

Section: Genetic Analysis Of the Loh Regionmentioning

confidence: 99%

The Japanese Wild-Derived Inbred Mouse Strain, MSM/Ms in Cancer Research

Okumura

Saito

Isogai

et al. 2021

Cancers

View full text Add to dashboard Cite

MSM/Ms is a unique inbred mouse strain derived from the Japanese wild mouse, Mus musculus molossinus, which has been approximately 1 million years genetically distant from standard inbred mouse strains mainly derived from M. m. domesticus. Due to its genetic divergence, MSM/Ms has been broadly used in linkage studies. A bacterial artificial chromosome (BAC) library was constructed for the MSM/Ms genome, and sequence analysis of the MSM/Ms genome showed approximately 1% of nucleotides differed from those in the commonly used inbred mouse strain, C57BL/6J. Therefore, MSM/Ms mice are thought to be useful for functional genome studies. MSM/Ms mice show unique characteristics of phenotypes, including its smaller body size, resistance to high-fat-diet-induced diabetes, high locomotive activity, and resistance to age-onset hearing loss, inflammation, and tumorigenesis, which are distinct from those of common inbred mouse strains. Furthermore, ES (Embryonic Stem) cell lines established from MSM/Ms allow the MSM/Ms genome to be genetically manipulated. Therefore, genomic and phenotypic analyses of MSM/Ms reveal novel insights into gene functions that were previously not obtained from research on common laboratory strains. Tumorigenesis-related MSM/Ms-specific genetic traits have been intensively investigated in Japan. Furthermore, radiation-induced thymic lymphomas and chemically-induced skin tumors have been extensively examined using MSM/Ms.

show abstract

“…Our study of the N ‐methyl‐ N ‐nitrosourea‐induced thymic lymphomas showed that susceptibility was affected by the D4Mit12 but not by the D5Mit7 locus. ( 53,54 ) This suggests that the two loci harbor different types of susceptibility genes.…”

Section: Toward Clues Of An Indirect Mechanism For Radiation Carcinogmentioning

confidence: 99%

Radiation carcinogenesis in mouse thymic lymphomas

Kominami

Niwa

2006

Cancer Science

View full text Add to dashboard Cite

Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the 'indirect mechanism' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. T he multi-step model of carcinogenesis defines cancer initiation as genomic change and promotion as the series of events leading to proliferation of initiated cells. Promoting factors can either be intrinsic or extrinsic to cells of the tumor cell lineage, and some promoting agents increase the probability that a cell will acquire additional mutations necessary for neoplastic progression. Analysis of activation of ras oncogenes after administrating a chemical carcinogen revealed that their activation is easily detectable before the onset of neoplasia, existing in apparently normal cells for long periods of time without inducing malignant transformation.(1,2) This suggests that initiation is a frequent event and only a few initiated cells proliferate for neoplastic progression. A quantitative study of common leukemia fusion genes in humans showed a consistent result.(3) It revealed that the fusion genes due to chromosome translocations, specific and stable markers for tracking leukemic clones, are detected in the blood of healthy newborns at a high rate that is significantly greater than that of the cumulative risk of the corresponding leukemia. These findings suggest that the factors that facilitate expansion of initiated cells with tumorigenic potential are important as well in determining cancer frequency.Ionizing radiation is a well-known carcinogen for a variety of human and mouse cells and tissues, and a complete carcinogen that is able to initiate and promote neoplastic progression. (4) Radiation can induce a broad spectrum of DNA lesions including damage to nucleotide bases, cross-linking, and DNA single-strand breaks and DSBs. Among these lesions, DSBs are the principal lesions of importance in the induction of both chromosomal abnormalities and gene mutations. Radiation effects or consequences are modulated by various secondary factors, inducing genomic instability that is probably the initiation of carcinogenesis. Analysis of molecular and structural changes associated with radiation-induced mutations shows that the spectrum of changes differs markedly from that for spontaneous or chemical-induced mutations. For instance, inactivation of the p53 tumor suppressor gene has been reported in a small fraction of radiation-induced mouse lymphomas ...

show abstract

The D5Mit7 locus on mouse chromosome 5 provides resistance to -ray-induced but not N-methyl-N-nitrosourea-induced thymic lymphomas

Cited by 12 publications

References 34 publications

Multilocus inheritance determines predisposition to α‐radiation induced bone tumourigenesis in mice

Multilocus inheritance determines predisposition to α‐radiation induced bone tumourigenesis in mice

The Japanese Wild-Derived Inbred Mouse Strain, MSM/Ms in Cancer Research

Radiation carcinogenesis in mouse thymic lymphomas

Contact Info

Product

Resources

About