Sensitivity to tumor development by TALEN-mediated Trp53 mutant genes in the susceptible FVB/N mice and the resistance C57BL/6 mice

Woo Bin Yun,Ki Taek Nam,Bo Ram Song,Jun Young Choi,Mi Lim Lee,Jin Ju Park,Byeong Cheol Kang,Ji Eun Kim,Han-Woong Lee,Dae Youn Hwang

doi:10.1186/s42826-021-00107-y

Woo Bin Yun, Ki Taek Nam + Show 8 more

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https://doi.org/10.1186/s42826-021-00107-y

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Abstract

BackgroundThis 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-Trp53em2Hwl/Korl and C57BL/6-Trp53em1Hwl/Korl knockout (KO) mice over 16 weeks.ResultsMost of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/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-Trp53em2Hwl/Korl KO mice, but were not detected in C57BL/6-Trp53em1Hwl/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-Trp53em2Hwl/Korl KO mice.ConclusionsOur results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/Korl KO mice over 16 weeks.

Highlights

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
The body weight of both genders was lower in the C57BL/6-Trp53em1Hwl/Korl KO mice than that observed in wild type (WT) mice, their statistical significance was only apparent in the female group (Fig. 2A)
Of the nine organs considered, only the spleen weight was dramatically increased FVB/N-Trp53em2Hwl/Korl KO mice compared with WT mice, while the thymus weight was significantly increased in C57BL/6-Trp53em1Hwl/Korl KO mice (Fig. 2B)

Summary

Introduction

This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp mutant gene Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53em2Hwl/Korl and C57BL/6-Trp53em1Hwl/Korl knockout (KO) mice over 16 weeks. Referred to as p53, the Trp proteins act as tumor suppressors in multicellular organisms and are encoded by homologous genes in various organisms, such as Trp (in mice) and TP53 (in humans) [1, 2] This protein prevents tumor cell growth at several points during the malignant process when it is under many types of stress, including DNA damage, oncogene activation, hypoxia, telomere attrition and deficiency of normal growth signal [3]. The comparison of tumorigenic sensitivity to TALEN-mediated Trp mutant gene in the tumor susceptible FVB/NJ mice and resistant C57BL/6 mice have never been considered, several comparative studies have compared the factors affecting cancer incidence in Trp deficient mice [14, 15]

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