• Title/Summary/Keyword: Knockout

검색결과 384건 처리시간 0.027초

Dynamics of ARF regulation that control senescence and cancer

  • Ko, Aram;Han, Su Yeon;Song, Jaewhan
    • BMB Reports
    • /
    • 제49권11호
    • /
    • pp.598-606
    • /
    • 2016
  • ARF is an alternative reading frame product of the INK4a/ARF locus, inactivated in numerous human cancers. ARF is a key regulator of cellular senescence, an irreversible cell growth arrest that suppresses tumor cell growth. It functions by sequestering MDM2 (a p53 E3 ligase) in the nucleolus, thus activating p53. Besides MDM2, ARF has numerous other interacting partners that induce either cellular senescence or apoptosis in a p53-independent manner. This further complicates the dynamics of the ARF network. Expression of ARF is frequently disrupted in human cancers, mainly due to epigenetic and transcriptional regulation. Vigorous studies on various transcription factors that either positively or negatively regulate ARF transcription have been carried out. However, recent focus on posttranslational modifications, particularly ubiquitination, indicates wider dynamic controls of ARF than previously known. In this review, we discuss the role and dynamic regulation of ARF in senescence and cancer.

치주질환의 면역학 (The Role of Immune Response in Periodontal Disease)

  • 김각균
    • IMMUNE NETWORK
    • /
    • 제3권4호
    • /
    • pp.261-267
    • /
    • 2003
  • The periodontal diseases are infections caused by bacteria in oral biofilm, a gelatinous mat commonly called dental plaque, which is a complex microbial community that forms and adhere to tooth surfaces. Host immune-pathogen interaction in periodontal disease appears to be a complex process, which is regulated not only by the acquired immunity to deal with ever-growing and -invading microorganisms in periodontal pockets, but also by genetic and/or environmental factors. However, our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host's immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system in fighting the virulent periodontal pathogens and in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response, in particular, $CD4^+$ T-cells plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host's tissue destruction.

Molecular imaging of atherosclerosis using reporter gene system

  • Yoo, Ran Ji;Lee, Kyochul;Kang, Joo Hyun;Lee, Yong Jin
    • 대한방사성의약품학회지
    • /
    • 제4권1호
    • /
    • pp.26-31
    • /
    • 2018
  • Macrophages play a key role in atherosclerotic plaque formation, but their participation has been discerned largely via ex vivo analyses of atherosclerotic lesions. Therefore, we aimed to identify atherosclerosis on noninvasive in vivo imaging using reporter gene system. This study demonstrated that recruitment of macrophages could be detected in atherosclerotic plaques of Apolipoprotein E knockout (ApoE-/-) mice with a sodium iodide symporter (NIS) gene imaging system using $^{99m}Tc-SPECT$. This novel approach to tracking macrophages to atherosclerotic plaques in vivo could have applications in studies of arteriosclerotic vascular disease.

The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes

  • Kim, Jinyoung;Lim, Yu-Mi;Lee, Myung-Shik
    • Molecules and Cells
    • /
    • 제41권1호
    • /
    • pp.11-17
    • /
    • 2018
  • Autophagy is critical for the maintenance of organelle function and intracellular nutrient environment. Autophagy is also involved in systemic metabolic homeostasis, and its dysregulation can lead to or accelerate the development of metabolic disorders. While the role of autophagy in the global metabolism of model organisms has been investigated mostly using site-specific genetic knockout technology, the impact of dysregulated autophagy on systemic metabolism has been unclear. Here, we review recent papers showing the role of autophagy in systemic metabolism and in the development of metabolic disorders. Also included are data suggesting the role of autophagy in human-type diabetes, which are different in several key aspects from murine models of diabetes. The results shown here support the view that autophagy modulation could be a new modality for the treatment of metabolic syndrome associated with lipid overload and human-type diabetes.

Recent Advances in Cloning Technology in the Pig -Review-

  • Miyoshi, K.;Sato, E.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제13권2호
    • /
    • pp.258-264
    • /
    • 2000
  • Production systems for cloned pigs are very important not only for an increase in production of superior animals but also for the production of knockout animals with organs that do not contain antigens for xenotransplantation or to analyze functions of isolated human genes. At present, however, effective systems have not been developed. We have tried to produce cloned pigs by transfering cultured cells into enucleated oocytes and obtained some cloned embryos. To develop a production system for cloned pigs, the basic technologies needed to support such an effort must be improved.

Biotechnologies for Improving Animal Metabolism and Growth - A Review

  • Chen, Daiwen
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제14권12호
    • /
    • pp.1794-1802
    • /
    • 2001
  • Biotechnology will play critical role in improving animal productivity. Animal growth rate and muscle deposition potential can be greatly improved by the application of biotechnology and biotechnological products. Administration of recombinant somatotropin (ST) or other compounds such as IGF-1 and growth hormone-releasing peptides (GHRPs) can enhance growth rate and carcass lean percentage. Gene transfer offers a powerful approach to manipulate endocrine system and metabolic pathways toward faster growth and better feed efficiency. Biotechnology is also extensively used for improving metabolism and activity of gut microorganisms for better nutrient digestibility. Knockout of growth-inhibiting genes such as myostatin results in considerable acceleration of body weight and muscle growth. Animal growth can also be improved by the use of gene therapy. Immunomodulation is another approach for efficient growth through controlling the activity of endogenous anabolic hormones. All the above aspects will be discussed in this review.

New role of E3 ubiquitin ligase in the regulation of necroptosis

  • Seo, Jinho;Lee, Eun-Woo;Song, Jaewhan
    • BMB Reports
    • /
    • 제49권5호
    • /
    • pp.247-248
    • /
    • 2016
  • Necroptosis is a well-known form of caspase-independent cell death. Necroptosis can be triggered by various extrinsic stimuli, including death ligands in the presence of receptorinteracting protein kinase 3 (RIPK3), a key mediator of necroptosis induction. Our recent studies have revealed that C-terminus HSC-70 interacting protein (CHIP), an E3 ligase, can function as an inhibitor of necroptosis. CHIP−/− mouse embryonic fibroblast showed higher sensitivity to necrotic stimuli than wild-type mouse embryonic fibroblast cells. Deleterious effects of CHIP knockout MEFs were retrieved by RIPK3 depletion. We found that CHIP negatively regulated RIPK3 and RIPK1 by ubiquitylation- and lysosome- dependent degradation. In addition, CHIP−/− mice showed postnatal lethality with intestinal defects that could be rescued by crossing with RIPK3−/− mice. These results suggest that CHIP is a negative regulator of RIPK1 and RIPK3, thus inhibiting necroptosis.

Somatic Cell Nuclear Transfer in Rodents, the Little Big Animals

  • Roh, Sangho
    • 한국수정란이식학회지
    • /
    • 제27권4호
    • /
    • pp.205-209
    • /
    • 2012
  • Transgenic rats and mice are useful experimental animal models for medical research including human disease model studies. Somatic cell nuclear transfer (SCNT) technology is successfully applied in most mammalian species including cattle, sheep, pig and mouse. SCNT is also considered to increase the efficacy of transgenic/knockout mouse and rat production. However, in the area of reproductive biotechnology, the rodent model is inadequate because of technical obstacles in manipulating the oocytes including intracytoplasmic sperm injection and SCNT. In particular, success of rat SCNT is very limited so far. In this review, the history of rodent cloning is described.

Overexpression of SMP30 Inhibit Radiation-Induced Apoptosis in Smad3-Knockout Mice Liver

  • Jeong, Da-Hee;Hong, Il-Hwa;Do, Sun-Hee;Yang, Hai-Jie;Yuan, Dong-Wei;Seo, Mi-Na;Jo, Jae-Chung;Lee, Seung-Sook;Jang, Won-Suk;Kim, Tae-Hwan;Jeong, Kyu-Shik
    • 한국수의병리학회:학술대회논문집
    • /
    • 한국수의병리학회 2005년도 Proceedings of The 2nd Asian Society of Veterinary Pathology Symposium(Vol.2) and 2005 Annual Meeting of The Korean Society of Veterinary Pathology(Vol.9)
    • /
    • pp.91.1-92
    • /
    • 2005
  • PDF

Suppression of Azoxymethane-Induced Colorectal Tumors in iNOS -/- C57BL/6J Mice.

  • Ahn, Byeong-Woo;Han, Beon-Seok;Jo, Hyun-Ye;Kang, Mi-Seung;Choi, Mi-Na;Kim, Dae-Joong;Nam, Sang-Yoong;Lee, Beom-Jun;Kim, Yun-Bae;Jang, Dong-Deuk
    • 한국수의병리학회:학술대회논문집
    • /
    • 한국수의병리학회 2005년도 Proceedings of The 2nd Asian Society of Veterinary Pathology Symposium(Vol.2) and 2005 Annual Meeting of The Korean Society of Veterinary Pathology(Vol.9)
    • /
    • pp.81-82
    • /
    • 2005
  • PDF