[摘要] 目的 研究ATM基因移除小鼠Sertoli细胞对于DNA双链断裂(DSB)损伤的修复作用。方法 将30只4～5周龄C57小鼠随机分为ATM敲除小鼠(n=15)和对照组(n=15),各组又分为无照射和0.1Gy电离辐射45min、2hr、24hr、48hr组，观察处死后睾丸组织DAPI、γ-H2Ax免疫荧光染色情况。结果 ATM-/-小鼠Sertoli细胞相对于ATM+/+小鼠生殖细胞对DSB损伤修复效率降低。结论 ATM-/-小鼠Sertoli细胞对于DSB损伤修复效率下降。
[Abstract] Objective To Study the repair of DNA double-strand break(DSB) in ATM-/- mice sertoli cells. Methods 30 4-5wk C57 male mice were randomly divided into ATM-/- mice group and control group,of which were randomly divided into 0.1Gy X-ray irradiation(ionizing irradiation)0 min,45min,2hr,24hr,48hr groups ,immunofluorescence staining of DAPI and γ-H2Ax were done. Results After low-dose irradiation,ATM-/- mice sertoli cells have a lower repair efficiency than wild type mice germ cells. Conclusion Efficiency of DSB repair in ATM-/- mice sertoli cells is lower than that of C57 mice.
[1] Takubo, K., Ohmura, M., Azuma, M., Nagamatsu, G., Yamada, W., Arai, F., . . . Suda, T. (2008). Stem cell defects in ATM-deficient undifferentiated spermatogonia through DNA damage-induced cell-cycle arrest. Cell Stem Cell, 2(2), 170-182. doi: 10.1016/j.stem.2007.10.023
[2] Podhorecka, M. (2009). [gamma H2AX in the recognition of DNA double-strand breaks]. Postepy Hig Med Dosw (Online), 63, 92-98.
[3] Chen, S. R., & Liu, Y. X. (2015). Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling. Reproduction, 149(4), R159-167. doi: 10.1530/rep-14-0481
[4] Hai Y, Hou J, Liu Y, Yang H, Li Z & He Z 2014 The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and permatogenesis. Seminars in Cell & Developmental Biology 29 66–75.
[5] Geert H, Henk B. Kal,Christoph H. Westphal,et al. Ataxia Telangiectasia Mutated Expression and Activation in the Testis1, BIOLOGY OF REPRODUCTION 70, 1206–1212 (2004)
[6] Lee J, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Toyokuni S,imura T, Nakano T, Ogura A & Shinohara T 2007 Akt mediates selfrenewal division of mouse spermatogonial stem cells. Development 134 1853–1859.
[7] Rübe CE, Zhang S, Miebach N, et al. Protecting the heritable genome: DNA damage response mechanisms in spermatogonial stem cells. DNA Repair (Amst). 2011 Feb 7;10(2):159-68
[8] Dufour, J. M., Rajotte, R. V., Korbutt, G. S., & Emerich, D. F. (2003). Harnessing the immunomodulatory properties of Sertoli cells to enable xenotransplantation in type I diabetes. Immunol Invest, 32(4), 275-297.
[9] van den Driesche S, Sharpe RM, Saunders PT & Mitchell RT ;Regulation of the germ stem cell niche as the foundation for adult spermatogenesis: a role for miRNAs? Seminars in Cell & Developmental Biology 29 76–83.
[10]Oatley, J. M., Avarbock, M. R., Telaranta, A. I., Fearon, D. T., & Brinster, R. L. (2006). Identifying genes important for spermatogonial stem cell self-renewal and survival. Proc Natl Acad Sci U S A, 103(25), 9524-9529. doi: 10.1073/pnas.0603332103
