Yun Woo Bin, Kim Ji Eun, Lee Mi Lim, Choi Jun Young, Park Jin Ju, Song Bo Ram, Kang Byeong Cheol, Nam Ki Taek, Lee Han-Woong, Hwang Dae Youn
Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science, Pusan National University, 50 Cheonghak-ri, Samnangjin-eup, Miryang-si, Gyeongsangnam-do, 50463, Korea.
Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul, 03722, South Korea.
Lab Anim Res. 2021 Nov 29;37(1):32. doi: 10.1186/s42826-021-00107-y.
This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53/Korl and C57BL/6-Trp53/Korl knockout (KO) mice over 16 weeks.
Most of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53/Korl KO mice than C57BL/6-Trp53/Korl KO mice, although there were significant differences in the body weight, immune organ weight, number of red blood cells, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), total bilirubin (Bil-T) and glucose (Glu) levels in the KO mice relative to the wild type (WT) mice. Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53/Korl KO mice, but were not detected in C57BL/6-Trp53/Korl KO mice. The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53/Korl KO mice.
Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53/Korl KO mice than C57BL/6-Trp53/Korl KO mice over 16 weeks.
本研究旨在比较转录激活样效应核酸酶(TALEN)介导的Trp53突变基因诱导肿瘤过程中小鼠品系的敏感性。在16周内,对FVB/N-Trp53/Korl和C57BL/6-Trp53/Korl基因敲除(KO)小鼠的致瘤表型改变进行评估,包括存活率、肿瘤形成和肿瘤谱。
尽管与野生型(WT)小鼠相比,基因敲除小鼠的体重、免疫器官重量、红细胞数量、平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)、平均红细胞血红蛋白浓度(MCHC)、血小板计数(PLT)、总胆红素(Bil-T)和葡萄糖(Glu)水平存在显著差异,但FVB/N-Trp53/Korl基因敲除小鼠的大多数生理表型因素高于C57BL/6-Trp53/Korl基因敲除小鼠。此外,在FVB/N-Trp53/Korl基因敲除小鼠体表皮肤的各个区域也观察到大量实体瘤,而在C57BL/6-Trp53/Korl基因敲除小鼠中未检测到。在两种Trp53基因敲除小鼠中最常观察到的肿瘤是恶性淋巴瘤,而软组织畸胎瘤和血管肉瘤仅在FVB/N-Trp53/Korl基因敲除小鼠中检测到。
我们的结果表明,在16周内,TALEN介导的Trp53突变基因诱导的肿瘤谱和发生率在FVB/N-Trp53/Korl基因敲除小鼠中比C57BL/6-Trp53/Korl基因敲除小鼠更大。