• Title/Summary/Keyword: Mouse models

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Mouse Models of Gastric Carcinogenesis

  • Yu, Sungsook;Yang, Mijeong;Nam, Ki Taek
    • Journal of Gastric Cancer
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    • v.14 no.2
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    • pp.67-86
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    • 2014
  • Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.

Genetically Engineered Mouse Models for Drug Development and Preclinical Trials

  • Lee, Ho
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.267-274
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    • 2014
  • 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.

Insights into granulosa cell tumors using spontaneous or genetically engineered mouse models

  • Kim, So-Youn
    • Clinical and Experimental Reproductive Medicine
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    • v.43 no.1
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    • pp.1-8
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    • 2016
  • Granulosa cell tumors (GCTs) are rare sex cord-stromal tumors that have been studied for decades. However, their infrequency has delayed efforts to research their etiology. Recently, mutations in human GCTs have been discovered, which has led to further research aimed at determining the molecular mechanisms underlying the disease. Mouse models have been important tools for studying GCTs, and have provided means to develop and improve diagnostics and therapeutics. Thus far, several genetically modified mouse models, along with one spontaneous mouse model, have been reported. This review summarizes the phenotypes of these mouse models and their applicability in elucidating the mechanisms of granulosa cell tumor development.

Mouse Gesture Design Based on Mental Model (심성모형 기반의 마우스 제스처 개발)

  • Seo, Hye Kyung
    • Journal of Korean Institute of Industrial Engineers
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    • v.39 no.3
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    • pp.163-171
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    • 2013
  • Various web browsers offer mouse gesture functions because they are convenient input methods. Mouse gestures enable users to move to the previous page or tab without clicking its relevant icon or menu of the web browser. To maximize the efficiency of mouse gestures, they should be designed to match users' mental models. Mental models of human beings are used to make accurate predictions and reactions when certain information has been recognized by humans. This means providing users with appropriate information about mental models will lead to fast understanding and response. A cognitive response test was performed in order to evaluate whether the mouse gestures easily associate with their respective functional meanings or not. After extracting mouse gestures which needed improvement, those were redesigned to reduce cognitive load via sketch maps. The methods presented in this study will be of help for evaluating and designing mouse gestures.

Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data

  • Kim, Jaewon;Rhee, Hwanseok;Kim, Jhingook;Lee, Sanghyuk
    • Genomics & Informatics
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    • v.18 no.1
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    • pp.3.1-3.8
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    • 2020
  • Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

Mouse models of breast cancer in preclinical research

  • Park, Mi Kyung;Lee, Chang Hoon;Lee, Ho
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.160-165
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    • 2018
  • 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.

Growth signaling and longevity in mouse models

  • Kim, Seung-Soo;Lee, Cheol-Koo
    • BMB Reports
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    • v.52 no.1
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    • pp.70-85
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    • 2019
  • Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.

Recent Progress in Transgenic Mouse Models as an Alternative Carcinogenicity Bioassay (형질전환 마우스 모델 발암성 평가의 최신 지견)

  • Son Woo-Chan;Kim Bae-Hwan;Jang Dong-Deuk;Kim Chull-Kyu;Han Beom-Seok;Kim Jong-Choon;Kang Boo-Hyon;Lee Je-Bong;Choi Yang-Kyu;Kim Hyoung-Chin
    • Toxicological Research
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    • v.21 no.1
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    • pp.1-14
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    • 2005
  • Transgenic mouse models have been introduced and accepted by regulatory bodies as an alternative to carcinogenicity assay models to predict and evaluate chemical carcinogens. The recent research outcomes in transgenic mouse models have made progressive advances in the understanding of chemical carcinogenesis and the evaluation of potential human carcinogens. However, these models still remain to be insufficient assay systems although the insufficiencies have been recognised and are being resolved. Based on up to date information from literature, this review article intends to understand currently accepted transgenic mouse models, issues arising from study design, interpretation of the study, results of validation project and their cancer prediction rate, and further perspectives of cancer assay models from the regulatory view point.

The Need for the Development of Pig Brain Tumor Disease Model using Genetic Engineering Techniques (유전자 조작기법을 통한 돼지 뇌종양 질환모델 개발의 필요성)

  • Hwang, Seon-Ung;Hyun, Sang-Hwan
    • Journal of Embryo Transfer
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    • v.31 no.1
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    • pp.97-107
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    • 2016
  • Although many diseases could be treated by the development of modern medicine, there are some incurable diseases including brain cancer, Alzheimer disease, etc. To study human brain cancer, various animal models were reported. Among these animal models, mouse models are valuable tools for understanding brain cancer characteristics. In spite of many mouse brain cancer models, it has been difficult to find a new target molecule for the treatment of brain cancer. One of the reasons is absence of large animal model which makes conducting preclinical trials. In this article, we review a recent study of molecular characteristics of human brain cancer, their genetic mutation and comparative analysis of the mouse brain cancer model. Finally, we suggest the need for development of large animal models using somatic cell nuclear transfer in translational research.

The use of animal models in rheumatoid arthritis research

  • Jin-Sun Kong;Gi Heon Jeong;Seung-Ah Yoo
    • Journal of Yeungnam Medical Science
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    • v.40 no.1
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    • pp.23-29
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    • 2023
  • The pathological hallmark of rheumatoid arthritis (RA) is a synovial pannus that comprises proliferating and invasive fibroblast-like synoviocytes, infiltrating inflammatory cells, and an associated neoangiogenic response. Animal models have been established to study these pathological features of human RA. Spontaneous and induced animal models of RA primarily reflect inflammatory aspects of the disease. Among various induced animal models, collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) models are widely used to study the pathogenesis of RA. Improved transplantation techniques for severe combined immunodeficiency (SCID) mouse models of RA can be used to evaluate the effectiveness of potential therapeutics in human tissues and cells. This review provides basic information on various animal models of RA, including CIA and CAIA. In addition, we describe a SCID mouse coimplantation model that can measure the long-distance migration of human RA synoviocytes and cartilage destruction induced by these cells.