Miao Jinxin, Li Rong, Wettere Arnaud J Van, Guo Haoran, Tabaran Alexandru-Flaviu, O'Sullivan M Gerald, Carlson Timothy, Scott Patricia M, Chen Kuisheng, Gao Dongling, Li Huixiang, Wang Yaohe, Wang Zhongde, Cormier Robert T
Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, Academy of Medical Sciences, Zhengzhou University, Henan, China.
J Carcinog. 2021 Oct 7;20:18. doi: 10.4103/jcar.jcar_18_21. eCollection 2021.
The tumor suppressor gene is the most commonly mutated gene in human cancers. Humans who inherit mutant alleles develop a wide range of early onset cancers, a disorder called Li-Fraumeni Syndrome (LFS). -deficient mice recapitulate most but not all of the cancer phenotypes observed in -deficient human cancers, indicating that new animal models may complement current mouse models and better inform on human disease development.
The recent application of CRISPR/Cas9 genetic engineering technology has permitted the emergence of golden Syrian hamsters as genetic models for wide range of diseases, including cancer. Here, the first cancer phenotype of knockout golden Syrian hamsters is described.
Hamsters that are homozygous for mutations become moribund on average ~ 139 days of age, while hamsters that are heterozygous become moribund at ~ 286 days. homozygous knockout hamsters develop a wide range of cancers, often synchronous and metastatic to multiple tissues, including lymphomas, several sarcomas, especially hemangiosarcomas, myeloid leukemias and several carcinomas. heterozygous mutants develop a more restricted tumor spectrum, primarily lymphomas.
Overall, hamsters may provide insights into how deficiency leads to cancer in humans and can become a new model to test novel therapies.
肿瘤抑制基因是人类癌症中最常发生突变的基因。携带突变等位基因的人会患多种早发性癌症，这种疾病称为李-佛美尼综合征（LFS）。基因缺陷的小鼠重现了基因缺陷人类癌症中观察到的大部分而非全部癌症表型，这表明新的动物模型可能补充当前的小鼠模型，并更好地为人类疾病发展提供信息。
CRISPR/Cas9基因工程技术的最新应用使得金黄地鼠成为包括癌症在内的多种疾病的遗传模型。在此，描述了基因敲除金黄地鼠的首个癌症表型。
基因纯合突变的仓鼠平均在约139日龄时濒死，而杂合仓鼠在约286日龄时濒死。基因纯合敲除仓鼠会患多种癌症，通常是同步发生且转移至多个组织，包括淋巴瘤、几种肉瘤，尤其是血管肉瘤、髓系白血病和几种癌。基因杂合突变体的肿瘤谱较窄，主要是淋巴瘤。
总体而言，仓鼠可能有助于深入了解基因缺陷如何导致人类患癌，并可成为测试新疗法的新模型。
