• Biomolecules & Therapeutics
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• 제30권3호
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• pp.238-245
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• 2022

Previous reports have demonstrated that genetic mechanisms greatly mediate responses to drugs of abuse, including methamphetamine (METH). The circadian gene Period 2 (Per2) has been previously associated with differential responses towards METH in mice. While the behavioral consequences of eliminating Per2 have been illustrated previously, Per2 overexpression has not yet been comprehensively described; although, Per2-overexpressing (Per2 OE) mice previously showed reduced sensitivity towards METH-induced addiction-like behaviors. To further elucidate this distinct behavior of Per2 OE mice to METH, we identified possible candidate biomarkers by determining striatal differentially expressed genes (DEGs) in both drug-naïve and METH-treated Per2 OE mice relative to wild-type (WT), through RNA sequencing. Of the several DEGs in drug naïve Per2 OE mice, we identified six genes that were altered after repeated METH treatment in WT mice, but not in Per2 OE mice. These results, validated by quantitative real-time polymerase chain reaction, could suggest that the identified DEGs might underlie the previously reported weaker METH-induced responses of Per2 OE mice compared to WT. Gene network analysis also revealed that Asic3, Hba-a1, and Rnf17 are possibly associated with Per2 through physical interactions and predicted correlations, and might potentially participate in addiction. Inhibiting the functional protein of Asic3 prior to METH administration resulted in the partial reduction of METH-induced conditioned place preference in WT mice, supporting a possible involvement of Asic3 in METH-induced reward. Although encouraging further investigations, our findings suggest that these DEGs, including Asic3, may play significant roles in the lower sensitivity of Per2 OE mice to METH.

• 한국어병학회지
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• 제35권2호
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• pp.157-165
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• 2022

Single-cycle viruses generated by reverse genetic technology are replication-incompetent viruses due to the elimination of gene(s) essential for viral replication, which provides a way to overcome the safety problem in attenuated viruses. Infectious hematopoietic necrosis virus (IHNV) is a major pathogen causing severe damage in cultured salmonid species. In the present study, we generated a single-cycle IHNV lacking the transmembrane and cytoplasmic domain in the G gene (rIHNV-GΔTM) and evaluated the prophylactic potential of rIHNV-GΔTM in rainbow trout (Oncorhynchus mykiss). To produce rIHNV-GΔTM, IHNV G protein-expressing Epithelioma papulosum cyprini (EPC) cells were established. However, as the efficiency of rIHNV-GΔTM production in EPC cell clones was not high, fish were immunized with a low-tittered single-cycle virus (1.5 × 10² PFU/fish). Despite the low dose, the single-cycle IHNV induced significant protection in rainbow trout against IHNV infection, suggesting high immunogenicity of rIHNV-GΔTM. No significant difference in serum ELISA titers against IHNV between the rIHNV-GΔTM immunized group and the control group suggests that the immunized dose of rIHNV-GΔTM might be too low to induce significant humoral adaptive immune responses in rainbow trout. The involvement of adaptive cellular immunity or innate immunity in the present significantly higher protection by the immunization with rIHNV-GΔTM should be further investigated to know the protection mechanism.

• Applied Biological Chemistry
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• 제38권4호
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• pp.313-319
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• 1995

본 실험은 알팔파(Medicago sativa) 근류균인 Rhizobium meliloti TAL1372 균주에서 섬유소분해효소의 활성을 확인하고 이 유전자를 크로닝하기 위해 코스미드 벡타인 pLAFR3를 사용하여 유전자 은행을 만들었다. 이 유전자 은행으로 부터 분리한 1,000개의 형질 도입체에서 CM-cellulase(carboxymethylcellulase) 활성이 있는 클론(pRC8-71) 하나를 분리하였으며 30kb 크기의 R. meliloti DNA 단편을 함유하고 있는 것을 확인하였다. 이 CM-cellulase 유전자의 발현 산물을 native PAGE 법에 의하여 분자량을 측정한 결과 약 45kD 정도의 크기로 추정되었으며 pRC8-71로 부터 Tn5 변이법에 의해 조사한 결과 30kb 단편 내에서 CM-cellulase 유전자의 위치는 제한효소 KpnI에 의해 절단되는 약 3kb 단편에 존재하였다. 표시교환 변이법에 의해 야생균주 R. meliloti TAL1372로부터 cellulase 무생산 변이체를 얻어 근류형성 정도를 실험한 결과 CM-cellulase유전자가 근류형성에 관련될 것으로 추정되었다.

• 생명과학회지
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• 제26권10호
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• pp.1137-1152
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• 2016

세포는 다양한 인체 질환에 관련되어 있는 저산소 환경을 인지하고 반응하며 적응한다. 저산소 상태에 적응하기 위해서는 hypoxic 유전자의 발현을 증가시키고 aerobic 유전자의 발현을 감소시키는 유전자 발현 조절이 필요하다. 최근 연구에서 미토콘드리아 호흡계가 이러한 유전자 발현 조절에 관여됨이 밝혀지고 있다. 본 연구에서는 호흡이 가능한 곰팡이(Saccharomyces cerevisiae)와 호흡이 불가능한 돌연변이 곰팡이를 실험대상으로 하여 미토콘드리아 호흡계가 저산소 환경에서 유전자 발현 조절에 관여됨을 DNA microarray 기법을 이용하여 전체 유전자를 대상으로 조사하였다. 산소 농도가 감소함에 반응하여 많은 유전자의 발현에 변화가 있었으며, 이러한 차별적인 발현 양상을 보이는 유전자는 여러 그룹으로 분류할 수 있었다. 대부분의 hypoxic 그리고 aerobic 유전자는 저산소 상태에 적응하는 발현 양상을 위해서는 미토콘드리아 호흡계가 필요하였다. 그러나 일부 hypoxic 그리고 aerobic 유전자는 미토콘드리아 호흡계와 무관하게 저산소 상태에 적응하는 발현 양상을 보였다. 이러한 결과는 미토콘드리아 호흡계가 저산소 환경에 적응하는 유전자 발현 조절에 필요하며, 또한 여러 기전을 통하여 이러한 유전자 발현 조절에 관여함을 제시한다. 또한 microarray 실험 결과에서 도출된 산소 농도에 대해 차별적인 발현을 보이는 유전자에 대하여 gene ontology 및 promoter 분석을 수행하였고 이러한 추가 분석 결과는 산소에 의해 조절되는 유전자와 함께 세포가 저산소 환경에 적응하는 기작을 이해하는 데 유용한 자료가 될 것으로 기대된다.

• BMB Reports
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• 제36권1호
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• pp.49-59
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• 2003

Platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. The vital functions of PDGFs for angiogenesis, as well as development of kidney, brain, cardiovascular system and pulmonary alveoli during embryogenesis, have been well demonstrated by gene knock-out approaches. Clinical studies reveal that aberrant expression of PDGF and its receptor is often associated with a variety of disorders including atherosclerosis, fibroproliferative diseases of lungs, kidneys and joints, and neoplasia. PDGF contributes to cancer development and progression by both autocrine and paracrine signaling mechanisms. In this review article, important features of the PDGF isoforms and their cell surface receptor subunits are discussed, with regards to signal transduction, PDGF-isoform specific cellular response, and involvement in angiogenesis, and tumorstromal interactions.

• Clinical and Experimental Pediatrics
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• 제56권10호
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• pp.456-458
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• 2013

Cystic fibrosis (CF) is a genetic disease with autosomal recessive inheritance and is common in Caucasian people. The prevalence of this disease is between 1/2,000 and 1/3,500 live births, and the incidence varies between populations. Although the CF transmembrane conductance regulator gene is expressed in the kidneys, renal involvement is rare. With advances in the treatment of CF, life expectancy has increased, and some previously unobserved disease associations are now seen in patients with CF. It is important to follow patients with CF for possible abnormalities that may accompany CF. In this paper, we present two rare cases of CF accompanied by nephrotic syndrome.

• Clinical and Experimental Reproductive Medicine
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• 제39권2호
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• pp.41-45
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• 2012

Transcription factors govern diverse aspects of cell growth and differentiation as major switches of gene expression. Etv5, a member of the E26 transformation-specific family of transcription factors, has many stories to share when it comes to reproduction. Etv5 deficient mice show complex infertility phenotypes both in males and females. In males, the infertility phenotype exhibited by Etv5 deficiency is sexually dimorphic, and it involves both somatic cells and germ cells. In $Etv5^{-/-}$ female mice, the problem is more complicated by hormonal involvement. This review synthesizes old and new information on this versatile transcription factor-from the inadvertent discovery of its role in the testes to its newly discovered role in maintaining spermatogonial stem cells.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.304.3-305
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• 2002

The present study investigated the passive avoidance and spatial learning in the ${\mu}$-opioid receptor gene knockout mice and wild type mice. In the step-through passive avoidance task. the ${\mu}$-opioid receptor knockout mice did not differ from the wild type mice. In Morris water maze. however. the ${\mu}$-opioid receptor knockout mice showed significant memory deficit compared to wild type mice. (omitted)

• Annals of Clinical Neurophysiology
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• 제22권1호
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• pp.29-32
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• 2020

Sarcoglycanopathies are a rare group of autosomal recessive limb-girdle muscular dystrophies (LGMDs) caused by genetic variants in α-, β-, γ-, or δ-sarcoglycan that maintain membrane integrity and contribute to molecular signal processing. High-throughput nucleotide sequencing was performed in patients with slowly progressive proximal muscle weakness from early childhood with respiratory involvement, which detected a novel homozygous nonsense variant (c.601C>T;p.Gln201Ter) in SGCB. This report informs about the clinical characteristics of LGMD2E (type-2E LGMD) in Korea and provides genetic confirmation of the disease.

• Molecules and Cells
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• 제42권12호
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• pp.828-835
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• 2019

PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. This review summarizes the neuronal functions of the PIWI-piRNA pathway in multiple animal species, including their involvement in axon regeneration, behavior, memory formation, and transgenerational epigenetic inheritance of adaptive memory. This review also discusses the consequences of dysregulation of neuronal PIWI-piRNA pathways in certain neurological disorders, including neurodevelopmental and neurodegenerative diseases. A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications.