• Title/Summary/Keyword: Animal models

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Longevity through diet restriction and immunity

  • Jeong-Hoon Hahm;Hyo-Deok Seo;Chang Hwa Jung;Jiyun Ahn
    • BMB Reports
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    • v.56 no.10
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    • pp.537-544
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    • 2023
  • The share of the population that is aging is growing rapidly. In an aging society, technologies and interventions that delay the aging process are of great interest. Dietary restriction (DR) is the most reproducible and effective nutritional intervention tested to date for delaying the aging process and prolonging the health span in animal models. Preventive effects of DR on age-related diseases have also been reported in human. In addition, highly conserved signaling pathways from small animal models to human mediate the effects of DR. Recent evidence has shown that the immune system is closely related to the effects of DR, and functions as a major mechanism of DR in healthy aging. This review discusses the effects of DR in delaying aging and preventing age-related diseases in animal, including human, and introduces the molecular mechanisms that mediate these effects. In addition, it reports scientific findings on the relationship between the immune system and DR-induced longevity. The review highlights the role of immunity as a potential mediator of the effects of DR on longevity, and provides insights into healthy aging in human.

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.

Animal Models of Alzheimer's Dementia (알쯔하이머 치매의 동물모형)

  • Woo, Sung-Il
    • Korean Journal of Biological Psychiatry
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    • v.6 no.2
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    • pp.149-152
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    • 1999
  • Transgenic mice models of Alzheimer's disease were produced by overexpressing APP(amyloid precursor protein) mutant and presenilin mutant genes using the promotors that induced neuronal expression. The neuropathologies, electrophysiological changes and behavioral changes that were demonstrated in these transgenic mice models were amyloid changes, gliotic changes, A-beta increases, deficit in LTP(long-term potentiation) and behavioral changes. Some or all of the above changes were found in each transgenic mice model. These models generally showed amyloid neuropathology but they usually lacked the neurofibrillary tangles. So, they can be regarded as partial models of Alzheimer's disease. The development of them is undoubtedly the great progress toward future research.

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Tempo of Diversification of Global Amphibians: One-Constant Rate, One-Continuous Shift or Multiple-Discrete Shifts?

  • Chen, Youhua
    • Animal Systematics, Evolution and Diversity
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    • v.30 no.1
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    • pp.39-43
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    • 2014
  • In this brief report, alternative time-varying diversification rate models were fitted onto the phylogeny of global amphibians by considering one-constant-rate (OCR), one-continuous-shift (OCS) and multiple-discrete- shifts (MDS) situations. The OCS diversification model was rejected by ${\gamma}$ statistic (${\gamma}=-5.556$, p<0.001), implying the existence of shifting diversification rates for global amphibian phylogeny. Through model selection, MDS diversification model outperformed OCS and OCR models using "laser" package under R environment. Moreover, MDS models, implemented using another R package "MEDUSA", indicated that there were sixteen shifts over the internal nodes for amphibian phylogeny. Conclusively, both OCS and MDS models are recommended to compare so as to better quantify rate-shifting trends of species diversification. MDS diversification models should be preferential for large phylogenies using "MEDUSA" package in which any arbitrary numbers of shifts are allowed to model.

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.

Evaluation of a cell enzyme-linked immunosorbent assay for the detection of Borna disease virus antibodies in experimentally infected animals (보르나 바이러스를 실험감염시킨 동물에서 항체검출에 대한 세포효소면역반응법의 평가에 대한 연구)

  • Lee, Du-sik
    • Korean Journal of Veterinary Research
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    • v.32 no.3
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    • pp.377-380
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    • 1992
  • The value of the cell enzyme-linked immunosorbent assay as a possible replacement for the indirect immunofluorescence antibody test for the estimation of antibodies against BD virus was assessed in four animal models. The serum antibody response was measured by both assay systems;the variability of both tests was less than one diluent step, and correlation of the two tests was assessed using regression analysis. The study showed that the all four animal models gave satisfactory correlation of CELISA and IFA. There, CELISA is acceptable for use in mouse, rabbit, chicken and rat models.

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Anti-pyretic and anti-inflammatory activity of chloroform extract of Croton roxburghii in standard animal models

  • Sivakumar, T;Rajavel, R;Karthikeyan, D;Duraisamy, R;Srinivasan, K;Kumar, S Suresh;Karki, Subhas S
    • Advances in Traditional Medicine
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    • v.8 no.3
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    • pp.252-259
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    • 2008
  • The chloroform extract of Croton roxburghii (Family: Euphorbiaceae) was evaluated for its antipyretic effects in Brewer's yeast induced hyperthermia in rats. The anti-inflammatory effect of the Croton roxburghii was also evaluated by using carrageenan, dextran, histamine, serotonin induced rat paw oedema and cotton pellet induced granuloma (chronic) models in rats. The chloroform extract of Croton roxburghii (CECR) exhibited significant anti-pyretic and anti-inflammatory effect at the dose 50, 100 and 200 mg/kg. Maximum inhibition (55.32%) was notedat the dose of 200 mg/kg after 3 h of drug treatment in carrageenan induced paw oedema, whereas the Indomethacin (standard drug) produced 61.33% of inhibition. The extract exhibited significant anti-inflammatory activity in dextran induced paw edema in a dose dependent manner. In the chronic model (cotton pellet induced granuloma) the CECR (200 mg/kg) and Indomethacin (10 mg/kg) showed decreased formation of granuloma tissue by 52.32% and 56.32% respectively. The extract also exhibited a significant antipyretic response in Brewer's yeast induced pyrexia in rats. Thus, the present study revealed that the CECR exhibited significant antipyretic and anti-inflammatory activity in the tested animal models.

Generation of knockout mouse models of cyclin-dependent kinase inhibitors by engineered nuclease-mediated genome editing

  • Park, Bo Min;Roh, Jae-il;Lee, Jaehoon;Lee, Han-Woong
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.264-269
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    • 2018
  • Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. Mice lacking the tumor suppressors $p16^{Ink4a}$ (Cdkn2a, cyclin-dependent kinase inhibitor 2a), $p19^{Arf}$ (an alternative reading frame product of Cdkn2a,), and $p27^{Kip1}$ (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. The $p16^{Ink4a}$ and $p19^{Arf}$ knockout mice were generated via transcription activator-like effector nucleases (TALENs), and $p27^{Kip1}$ knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). These gene editing technologies were targeted to the first exon of each gene, to induce frameshifts producing premature termination codons. Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA.

Clinical profile of Asian and African strains of Zika virus in immunocompetent mice

  • Shin, Minna;Kim, Jini;Park, Jeongho;Hahn, Tae-Wook
    • Korean Journal of Veterinary Research
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    • v.61 no.2
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    • pp.12.1-12.9
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    • 2021
  • The mosquito-borne pathogen Zika virus may result in neurological disorders such as Guillain-Barré syndrome and microcephaly. The virus is classified as a member of the Flaviviridae family and its wide spread in multiple continents is a significant threat to public health. So, there is a need to develop animal models to examine the pathogenesis of the disease and to develop vaccines. To examine the clinical profile during Zika virus infection, we infected neonatal and adult wild-type mice (C57BL/6 and Balb/c) and compared the clinical signs of African-lineage strain (MR766) and Asian-lineage strain (PRVABC59, MEX2-81) of Zika virus. Consistent with previous reports, eight-week-old female Balb/c mice infected with these viral strains showed no changes in body weight, survival rate, and neurologic signs, but demonstrated increases in the weights of spleens and hearts. However, one-day-old neonates showed significantly lower survival rate and body weight with the African-lineage strain than the Asian-lineage strain. These results confirmed the pathogenic differences between Zika virus strains. We also evaluated the clinical responses in neonatal and adult mice of different strains. Our findings suggest that these are useful mouse models for characterization of Zika virus for vaccine development.

The effect of ginsenosides on depression in preclinical studies: A systematic review and meta-analysis

  • Kim, Yunna;Cho, Seung-Hun
    • Journal of Ginseng Research
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    • v.45 no.3
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    • pp.420-432
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    • 2021
  • Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.