Transformation Models for Characterization of Cancer Driver Genes / 中国生物化学与分子生物学报

The development of cancer is a complex process. Although many genetic and epigenetic alterations are detected in cancer cells, only small proportion of these alterations may function as cancer drivers. Because it is difficult to directly characterize driver factors in human body, alternative research models have continuously been developed. In the early stage from 1915 to 1980s, genetic activation of proto-oncogenes and inactivation of tumor suppressor genes were often characterized using various carcinogenicity tests, including animal tumor induction models, malignant transformation of normal human cells/tissues/organs cultured in vitro or transplanted into immuno-defected mice. Since 1990 to now, gene transfection and knockout technologies were frequently used to characterize cancer driver genes. Currently, 2-dimensional (2D) or 3-dimensional (3D) cell culture and organoid are also employed to test carcinogenicity of environmental factors and driver genes. In this review, we summarized the main models of malignant transformation and their advantages and disadvantages.

Mouse models of breast cancer in preclinical research / 한국실험동물학회지

Breast cancer remains the second leading cause of cancer death among woman, worldwide, despite advances in identifying novel targeted therapies and the development of treating strategies. Classification of clinical subtypes (ER+, PR+, HER2+, and TNBC (Triple-negative)) increases the complexity of breast cancers, which thus necessitates further investigation. Mouse models used in breast cancer research provide an essential approach to examine the mechanisms and genetic pathway in cancer progression and metastasis and to develop and evaluate clinical therapeutics. In this review, we summarize tumor transplantation models and genetically engineered mouse models (GEMMs) of breast cancer and their applications in the field of human breast cancer research and anti-cancer drug development. These models may help to improve the knowledge of underlying mechanisms and genetic pathways, as well as creating approaches for modeling clinical tumor subtypes, and developing innovative cancer therapy.

Targeted suppression of Act1 in the macrophages ameliorates experimental ulcerative colitis in mice induced by dextran sodium sulfate / 中国实验动物学报

Objective To investigate the role of macrophage?derived Act1 (nuclear factor kappa B activator 1) in the inflammatory bowel disease. Methods Genetically engineered mice carrying targeted suppression of Act1 in the mac?rophages (Anti?Act1) were used for the dextran sodium sulfate (DSS)?induced ulcerative colitis. The severity of colitis was assessed by weight loss, stool consistency, fecal blood index, colorectal length and H&E histology. The infiltration of CD45 + leukocytes and CD68 + macrophages in the inflammatory intestine was observed by immunohistochemical staining and expression levels of mRNA for inflammatory cytokines in colon tissues were analyzed by RT?qPCR. Results As com?pared with C57 mice, the anti?Act1 mice exhibited less severe acute colitis following DSS treatment, with reduced CD45 +leukocyte and CD68 + macrophage infiltrates in the colon tissue. Inflamed colons of the anti?Act1 mice expressed lower mR?NA levels of TNF?α, IL?1βand IL?6. Conclusions Targeted suppression of Act1 in the macrophages ameliorates dextran sodium sulfate?induced intestinal inflammation.

Genetically Engineered Mouse Models for Drug Development and Preclinical Trials

Drug development and preclinical trials are challenging processes and more than 80% to 90% of drug candidates fail to gain approval from the United States Food and Drug Administration. Predictive and efficient tools are required to discover high quality targets and increase the probability of success in the process of new drug development. One such solution to the challenges faced in the development of new drugs and combination therapies is the use of low-cost and experimentally manageable in vivo animal models. Since the 1980's, scientists have been able to genetically modify the mouse genome by removing or replacing a specific gene, which has improved the identification and validation of target genes of interest. Now genetically engineered mouse models (GEMMs) are widely used and have proved to be a powerful tool in drug discovery processes. This review particularly covers recent fascinating technologies for drug discovery and preclinical trials, targeted transgenesis and RNAi mouse, including application and combination of inducible system. Improvements in technologies and the development of new GEMMs are expected to guide future applications of these models to drug discovery and preclinical trials.

Extracting Extra-Telomeric Phenotypes from Telomerase Mouse Models

Telomerase reverse transcriptase (TERT) is the protein component of telomerase and combined with an RNA molecule, telomerase RNA component, forms the telomerase enzyme responsible for telomere elongation. Telomerase is essential for maintaining telomere length from replicative attrition and thus contributes to the preservation of genome integrity. Although diverse mouse models have been developed and studied to prove the physiological roles of telomerase as a telomere-elongating enzyme, recent studies have revealed non-canonical TERT activities beyond telomeres. To gain insights into the physiological impact of extra-telomeric roles, this review revisits the strategies and phenotypes of telomerase mouse models in terms of the extra-telomeric functions of telomerase.