adj.

遺伝子導入の、形質転換の、遺伝子組換えの、トランスジェニック

関: congenic、gene transfer、genetic transformation、Tg、transform、transformation、transforming、transgenesis、transgenically

WordNet

(mathematics) a function that changes the position or direction of the axes of a coordinate system
the act of changing in form or shape or appearance; "a photograph is a translation of a scene onto a two-dimensional surface" (同)translation
(genetics) modification of a cell or bacterium by the uptake and incorporation of exogenous DNA
a qualitative change (同)transmutation, shift
a rule describing the conversion of one syntactic structure into another related syntactic structure
subject to a mathematical transformation
change in outward structure or looks; "He transformed into a monster"; "The salesman metamorphosed into an ugly beetle" (同)transmute, metamorphose
change or alter in form, appearance, or nature; "This experience transformed her completely"; "She transformed the clay into a beautiful sculpture"; "transubstantiate one element into another" (同)transmute, transubstantiate
change (a bacterial cell) into a genetically distinct cell by the introduction of DNA from another cell of the same or closely related species
convert (one form of energy) to another; "transform energy to light"
increase or decrease (an alternating current or voltage)

PrepTutorEJDIC

変形,変質;変身 / (物理学で)変換;(電流の)変圧 / (言吾学で)変形
(別の形・外見・性質・状態などに)…‘を'『変える』,変化させる《+名+into+名》 / (物理・化学で)〈あるエネルギー〉‘を'他のエネルギーに変換する;〈電流〉‘を'変圧する

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/21 11:30:18」(JST)

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Transgenesis is the process of introducing an exogenous gene — called a transgene — into a living organism so that the organism will exhibit a new property and transmit that property to its offspring. Transgenesis can be facilitated by liposomes, plasmid vectors, viral vectors, pronuclear injection, protoplast fusion, and ballistic DNA injection.

Transgenic organisms are able to express foreign genes because the genetic code is similar for all organisms. This means that a specific DNA sequence will code for the same protein in all organisms. Due to this similarity in protein sequence, scientists can cut DNA at these common protein points and add other genes. An example of this is the "super mice" of the 1980s. These mice were able to produce the human protein tPA to treat blood clots.

1 Using plasmids from bacteria
2 Gene transfer technology
- 2.1 DNA microinjection
- 2.2 Retrovirus-mediated gene transfer
- 2.3 Stem cell transgenesis
  - 2.3.1 Multipotent stem cell transgenesis
  - 2.3.2 Pluripotent stem cell transgenesis
  - 2.3.3 Totipotent stem cell transgenesis
3 Applications
- 3.1 Pharming
- 3.2 Medical
4 Ethical concerns
5 Diagram
6 References

Using plasmids from bacteria

The most common type of transgenesis research is done with bacteria and viruses which are able to replicate foreign DNA.^[1] The plasmid DNA is cut using restriction enzymes, while the DNA to be copied is also cut with the same restriction enzyme, producing complementary sticky-ends. This allows the foreign DNA to hybridise with the plasmid DNA and be sealed by DNA ligase enzyme, creating a genetic code not normally found in nature. Altered DNA is inserted into plasmids for replication.^[2]

Gene transfer technology

DNA microinjection

The Desired gene construct is injected in the pronucleus of a reproductive cell using a glass needle around 0.5 to 5 micrometers in diameter. The manipulated cell is cultured in vitro to develop to a specific embryonic phase, is then transferred to a recipient female. DNA microinjection does not have a high success rate (roughly 2% of all injected subjects), even if the new DNA is incorporated in the genome, if it is not accepted by the germ-line the new traits will not appear in their offspring. If DNA is injected in multiple sites the chances of over-expression increase.^[3]

Retrovirus-mediated gene transfer

A retrovirus is a virus that carries its genetic material in the form of RNA rather than DNA. Retroviruses are used as vectors to transfer genetic material into the host cell. The result is a chimera, an organism consisting of tissues or parts of diverse genetic constitution. Chimeras are inbred for as many as 20 generations until homozygous genetic offspring are born.^[3]

Stem cell transgenesis

Multipotent stem cell transgenesis

Multipotent stem cells can only differentiate into a limited number of therapeutically useful cell types, nevertheless their safety and relative lack of complexity to us have resulted in the vast majority of current personalized cellular therapeutics involving multipotent stem cells (typically mesenchymal stem cells from adipose tissue).^[4]

Pluripotent stem cell transgenesis

Transgenic vectors can be delivered randomly^{[citation needed]}, or targeted to a specific genomic location, such as a safe harbor^{[citation needed]}. Scientists have performed research and technology development to provide the tools necessary to permit safe and effective pluripotent stem cell (PSC) transgenesis.^[5]^[6]^[7]^[8]^[9]^[10]^[11]^[12]

Totipotent stem cell transgenesis

The manipulated gene construct is inserted into totipotent stem cells, cells which can develop into any specialized cell. Cells containing the desired DNA are incorporated into the host’s embryo, resulting in a chimeric animal. Unlike the other two methods of injection which require live transgenic offspring for testing, embryonic cell transfer can be tested at the cell stage.

Applications

Pharming

Pharming is a portmanteau of "farming" and "pharmaceutical" and refers to the use of genetic engineering to insert genes that code for useful pharmaceuticals into host animals or plants that would otherwise not express those genes, thus creating a genetically modified organism (GMO). Pharming has gained application in biotechnology since the development of trangsgenic "super mice" in 1982. "Super mice" were genetically altered to produce the human drug, tPA (tissue plasminogen activator to treat blood clots), in 1987.^[2] Since then "super mice" pharming has come a long way. Using RNA interference scientists have produced a cow whose milk contains increased amounts of casein, a protein used to make cheese and other foods, and almost no beta-lactoglobulin, a component in milk whey protein that causes allergies.^[13]

"Pharming Examples:"^[14]

Haemoglobin as a blood substitute
human protein C anticoagulant
alpha-1 antitrypsin (AAT) for treatment of AAT deficiency
insulin for diabetes treatment
vaccines (antigens)
growth hormones for treatment of deficiencies
factor VIII blood clotting factor
factor IX blood clotting factor
fibrinogen blood clotting factor
lactoferrin as an infant formula additive

Medical

Transgenesis can be used to neutralize genes that would normally prevent xenotransplantation. For example, a protein found in pigs can cause humans to reject their transplanted organs. This protein can be replaced by a similar human genome to prevent the rejection.^[15]

Ethical concerns

Transgenesis has created certain ethical concerns. Examples include rights for animals that have been improved intellectually, legal ramifications, and possible health risks.^[16]

Diagram

A diagram comparing the genetic changes achieved through conventional plant breeding, transgenesis and cisgenesis

.

Note: New genotypes created with transgenic technologies also require multiple backcrossings. Furthermore, backcrossing does not account for the majority of time required to create, field test and release/commercialize a new variety.

References

^ "Mousepox Case Study — Module 4.0". Federation of American Scientists. History of Transgenics. Archived from the original on July 15, 2007.
^ ^a ^b Redway, Keith. "Transgenic organisms". Gene Manipulation & Recombinant DNA. University of Westminster. Retrieved June 28, 2014.
^ ^a ^b Margawati, Endang Tri (January 2003). "Transgenic Animals: Their Benefits To Human Welfare". Actionbioscience. Retrieved June 29, 2014.
^ clinicaltrials.org
^ Capecchi MR (June 2005). "Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century". Nat. Rev. Genet. 6 (6): 507–12. doi:10.1038/nrg1619. PMID 15931173.
^ Cong L, Ran FA, Cox D et al. (February 2013). "Multiplex genome engineering using CRISPR/Cas systems". Science 339 (6121): 819–23. doi:10.1126/science.1231143. PMC 3795411. PMID 23287718.
^ DiCarlo JE, Norville JE, Mali P, Rios X, Aach J, Church GM (April 2013). "Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems". Nucleic Acids Res. 41 (7): 4336–43. doi:10.1093/nar/gkt135. PMC 3627607. PMID 23460208.
^ Friedland AE, Tzur YB, Esvelt KM, Colaiácovo MP, Church GM, Calarco JA (August 2013). "Heritable genome editing in C. elegans via a CRISPR-Cas9 system". Nat. Methods 10 (8): 741–3. doi:10.1038/nmeth.2532. PMC 3822328. PMID 23817069.
^ Hwang WY, Fu Y, Reyon D et al. (March 2013). "Efficient genome editing in zebrafish using a CRISPR-Cas system". Nat. Biotechnol. 31 (3): 227–9. doi:10.1038/nbt.2501. PMC 3686313. PMID 23360964.
^ Nguyen HN, Reijo Pera RA (2008). "Metaphase spreads and spectral karyotyping of human embryonic stem cells". CSH Protoc: pdb.prot5047. PMID 21356916.
^ Mali P, Yang L, Esvelt KM et al. (February 2013). "RNA-guided human genome engineering via Cas9". Science 339 (6121): 823–6. doi:10.1126/science.1232033. PMC 3712628. PMID 23287722.
^ Xue H, Wu J, Li S, Rao MS, Liu Y (March 2014). "Genetic Modification in Human Pluripotent Stem Cells by Homologous Recombination and CRISPR/Cas9 System". Methods Mol. Biol. doi:10.1007/7651_2014_73. PMID 24615461.
^ Lopatto, Elizabeth (October 1, 2012). "Gene-Modified Cow Makes Milk Rich in Protein, Study Finds". Bloomberg Businessweek (New York City).
^ Buy M (1997). "Transgenic Animals". CCAC Resource Supplement. Canadian Council on Animal Care (CCAC).
^ "Actionbioscience | Transgenic Animals: Their Benefits To Human Welfare". actionbioscience.org. Retrieved November 29, 2014.
^ "Actionbioscience | Ethical Issues in Genetic Engineering and Transgenics". actionbioscience.org. Retrieved November 29, 2014.

UpToDate Contents

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1. 遺伝学およびゲノミクスのためのツール：研究用に育種された遺伝子改変マウス tools for genetics and genomics specially bred and genetically engineered mice
2. 慢性骨髄性白血病の細胞生物学および分子生物学 cellular and molecular biology of chronic myeloid leukemia
3. 筋萎縮性側索硬化症の病態修飾療法 disease modifying treatment of amyotrophic lateral sclerosis
4. 筋萎縮性側索硬化症の疫学および病因 epidemiology and pathogenesis of amyotrophic lateral sclerosis
5. 運動単位数推定法（MUNE） motor unit number estimation mune

English Journal

Flanking sequence determination and specific PCR identification of transgenic wheat b102-1-2.

Cao J, Xu J, Zhao T, Cao D, Huang X, Zhang P, Luan F.Author information a Liaoning Entry-Exit Inspection and Quarantine Bureau , Dalian , China.AbstractThe exogenous fragment sequence and flanking sequence between the exogenous fragment and recombinant chromosome of transgenic wheat B102-1-2 were successfully acquired using genome walking technology. The newly acquired exogenous fragment encoded the full-length sequence of transformed genes with transformed plasmid and corresponding functional genes including ubi, vector pBANF-bar, vector pUbiGUSPlus, vector HSP, reporter vector pUbiGUSPlus, promoter ubiquitin, and coli DH1. A specific polymerase chain reaction (PCR) identification method for transgenic wheat B102-1-2 was established on the basis of designed primers according to flanking sequence. This established specific PCR strategy was validated by using transgenic wheat, transgenic corn, transgenic soybean, transgenic rice, and non-transgenic wheat. A specifically amplified target band was observed only in transgenic wheat B102-1-2. Therefore, this method is characterized by high specificity, high reproducibility, rapid identification, and excellent accuracy for the identification of transgenic wheat B102-1-2.
Preparative biochemistry & biotechnology.Prep Biochem Biotechnol.2014 Apr 3;44(3):257-65. doi: 10.1080/10826068.2013.812563.
The exogenous fragment sequence and flanking sequence between the exogenous fragment and recombinant chromosome of transgenic wheat B102-1-2 were successfully acquired using genome walking technology. The newly acquired exogenous fragment encoded the full-length sequence of transformed genes with tr
PMID 24274014

An innovative and integrated approach based on DNA walking to identify unauthorised GMOs.

Fraiture MA, Herman P, Taverniers I, De Loose M, Deforce D, Roosens NH.Author information Scientific Institute of Public Health (WIV-ISP), Platform of Biotechnology and Molecular Biology (PBB), J. Wytsmanstraat 14, 1050 Brussels, Belgium; Scientific Institute of Public Health (WIV-ISP), Biosafety and Biotechnology Unit (SBB), J. Wytsmanstraat 14, 1050 Brussels, Belgium; Institute for Agricultural and Fisheries Research (ILVO), Technology and Food Sciences Unit, Burg. Van Gansberghelaan 115, bus 1, 9820 Merelbeke, Belgium; University of Gent (UGent), Faculty of Pharmaceutical Sciences, Laboratory of Pharmaceutical Biotechnology, Harelbekestraat 72, 9000 Ghent, Belgium.AbstractIn the coming years, the frequency of unauthorised genetically modified organisms (GMOs) being present in the European food and feed chain will increase significantly. Therefore, we have developed a strategy to identify unauthorised GMOs containing a pCAMBIA family vector, frequently present in transgenic plants. This integrated approach is performed in two successive steps on Bt rice grains. First, the potential presence of unauthorised GMOs is assessed by the qPCR SYBR®Green technology targeting the terminator 35S pCAMBIA element. Second, its presence is confirmed via the characterisation of the junction between the transgenic cassette and the rice genome. To this end, a DNA walking strategy is applied using a first reverse primer followed by two semi-nested PCR rounds using primers that are each time nested to the previous reverse primer. This approach allows to rapidly identify the transgene flanking region and can easily be implemented by the enforcement laboratories.
Food chemistry.Food Chem.2014 Mar 15;147:60-9. doi: 10.1016/j.foodchem.2013.09.112. Epub 2013 Sep 29.
In the coming years, the frequency of unauthorised genetically modified organisms (GMOs) being present in the European food and feed chain will increase significantly. Therefore, we have developed a strategy to identify unauthorised GMOs containing a pCAMBIA family vector, frequently present in tran
PMID 24206686

A model of liver carcinogenesis originating from hepatic progenitor cells with accumulation of genetic alterations.

Kim SK, Nasu A, Komori J, Shimizu T, Matsumoto Y, Minaki Y, Kohno K, Shimizu K, Uemoto S, Chiba T, Marusawa H.Author information Department of Gastroenterology and Hepatology, Graduate School of MedicineKyoto University, Kyoto, Japan.AbstractActivation-induced cytidine deaminase (AID) contributes to inflammation-associated carcinogenesis through its mutagenic activity. In our study, by taking advantage of the ability of AID to induce genetic aberrations, we investigated whether liver cancer originates from hepatic stem/progenitor cells that accumulate stepwise genetic alterations. For this purpose, hepatic progenitor cells enriched from the fetal liver of AID transgenic (Tg) mice were transplanted into recipient "toxin-receptor mediated conditional cell knockout" (TRECK) mice, which have enhanced liver regeneration activity under the condition of diphtheria toxin treatment. Whole exome sequencing was used to determine the landscape of the accumulated genetic alterations in the transplanted progenitor cells during tumorigenesis. Liver tumors developed in 7 of 11 (63.6%) recipient TRECK mice receiving enriched hepatic progenitor cells from AID Tg mice, while no tumorigenesis was observed in TRECK mice receiving hepatic progenitor cells of wild-type mice. Histologic examination revealed that the tumors showed characteristics of hepatocellular carcinoma and partial features of cholangiocarcinoma with expression of the AID transgene. Whole exome sequencing revealed that several dozen genes acquired single nucleotide variants in tumor tissues originating from the transplanted hepatic progenitor cells of AID Tg mice. Microarray analyses revealed that the majority of the mutations (>80%) were present in actively transcribed genes in the liver-lineage cells. These findings provided the evidence suggesting that accumulation of genetic alterations in fetal hepatic progenitor cells progressed to liver cancers, and the selection of mutagenesis depends on active transcription in the liver-lineage cells.
International journal of cancer. Journal international du cancer.Int J Cancer.2014 Mar 1;134(5):1067-76. doi: 10.1002/ijc.28445. Epub 2013 Sep 16.
Activation-induced cytidine deaminase (AID) contributes to inflammation-associated carcinogenesis through its mutagenic activity. In our study, by taking advantage of the ability of AID to induce genetic aberrations, we investigated whether liver cancer originates from hepatic stem/progenitor cells
PMID 23959426

Japanese Journal

A potential function for neuronal exosomes : Sequestering intracerebral amyloid-beta peptide

Yuyama Kohei,Sun Hui,Usuki Seigo,Sakai Shota,Hanamatsu Hisatoshi,Mioka Tetsuo,Kimura Nobuyuki,Okada Megumi,Tahara Hidetoshi,Furukawa Jun-ichi,Fujitani Naoki,Shinohara Yasuro,Igarashi Yasuyuki
FEBS letters 589(1), 84-88, 2015-01-02
… We demonstrated the presence of exosome-associated A beta in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. … Infusion of neuronal exosomes into brains of APP transgenic mice decreased A beta and amyloid depositions, similarly to what reported previously on neuroblastoma-derived exosomes. …
NAID 120005537475

A novel imprinted transgene located near a repetitive element that exhibits allelic imbalance in DNA methylation during early development

Uchiyama Koji,Watanabe Daisuke,Hayasaka Michiko [他]
Development, growth & differentiation 56(9), 653-668, 2014-12
NAID 40020329309

Horticultural characterization of a tetraploid transgenic plant of Tricyrtis sp. carrying the gibberellin 2-oxidase gene

Otani Masahiro,Ishibe Mitsuyo,Inthima Phithak [他]
Plant Biotechnology 31(4), 335-340, 2014-12
NAID 40020313518

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★リンクテーブル★

リンク元	「transform」「遺伝子導入」「congenic」「Tg」「gene transfer」
拡張検索	「transgenic mouse model」「transgenic plant」「transgenic animal」「transgenic founder animal」