2000 Fiscal Year Final Research Report Summary
Generation of knockout mice for Nijmegen breakage syndrome gene, NBS1.
| Project/Area Number |
11138237
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Research Institution | Hiroshima University |
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Principal Investigator |
MATSUURA Shinya Research Institute for Radiation Biology and Medicine, Hiroshima University, Associate Professor, 原爆放射能医学研究所, 助教授 (90274133)
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| Co-Investigator(Kenkyū-buntansha) |
TAUCHI Hiroshi Research Institute for Radiation Biology and Medicine, Hiroshima University, Research Associate, 原爆放射能医学研究所, 助手 (70216597)
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| Project Period (FY) |
1999
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| Keywords | Nijmegen syndrome / Cancer prone disease / Ataxia-telangiectasia / Rodiation sensitivity / Gene targeting / Model mouse / Embryonic lethal / Nbs1 |
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| Research Abstract |
Nijmegen breakage syndrome is an autosomal recessive disorder characterized by combined immunodeficiency, predisposition to cancer, microcephaly, and growth retardation. Cells from Nijmegen breakage syndrome display chromosomal instability, radiation sensitivity, and radioresistant DNA synthesis. An Nbs1 targeting vector was constructed and was introduced into mouse ES cells by electroporation. G418 resistant ES cell clones were selected and were screened for homologous recombination by Southern blot analysis. Out of 234 clones, 3 clones showed correct recombination and were used for blastocyst injection. Chimeric mice were back crossed with C57BL/6, and F1 mice were generated. PCR analysis demonstrated germ line transmission of the Nbs 1 mutant allele. Although the Nbs1 heterozygous mice were normal and fertile, Nbs1 null mice could not be obtained so far. The result suggested that the disruption of Nbs1 could cause embryonic lethality, indicating that Nbs1 protein complex is essential for viability. We are setting up timed matings to investigate the cause of embryonic lethality, and also trying to establish Nbs1 nullizygous fibroblasts to define further function of the Nbs1 gene.
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Research Products
(9 results)
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[Publications] Ito A., Tauchi, H., Kobayashi, J., Morishima, K., Nakamura, A., Hirokawa, Y., Matsuura, S., Ito, K., Komatsu, K.: "Expression of full-length NBS1 protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients."Biochem.Biophys.Res.Commun.. 265. 716-721 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Tauchi, H., Matsuura, S., Isomura, M., Kinjo, T., Nakamura, A., Sakamoto, S., Kondo, N., Endo, S., Komatsu, K., and Nakamura, Y.: "Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21, which contains the Nijmegen breakage syndrome gene, NBS1."Genomics.. 55. 242-247 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Hiramoto, T., Nakanishi, T., Sumiyoshi, T., Fukuda, T., Matsuura, S., Tauchi, H., Komatsu, K., Shibasaki, Y., Inui, H., Watatani, M., Yasutomi, M., Sumii, M., Kajiyama, G., Kamaka, N., Miyagawa, K., and Kamiya, K.: "Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer."Oncogene. 18. 3422-3426 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakamura, A., Matsuura, S., Tauchi, H., Hanada, R., Ohashi, H., Hasegawa, T., Honda, K., Masuno, M., Imaizumi, K., Sugita, K., Ide, T., and Komatsu, K.: "Four novel mutations of the Fanconi anemia group A gene (FAA) in Japanese patients."J.Hum.Genet.. 44. 48-51 (1999)
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「研究成果報告書概要(欧文)」より
