gene-targeting
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... Table of Contents -- Chapter 1 -- Gene Targeting 1 -- Wolf M. ... ... Waldman -- Chapter 3 -- Gene Targeting in Tripanosomatids 65 -- Angela K. ... ... Cruz -- Chapter 4 -- Gene Targeting in Plants 83 -- Remko Offringa and Paul Hooykaas -- Chapter 5 -- ... ... Gene Targeting in Mammalian Development and Physiology 123 -- Thomas Lufkin -- Chapter 6 -- Animal Models ... ... Zarling -- Chapter 8 -- Gene Targeting in Human Gene Therapy 211 -- Manuel A. Vega -- Index -- 231 ...
236 stran : ilustrace ; 24 cm
- MeSH
- genový targeting MeSH
- Konspekt
- Obecná genetika. Obecná cytogenetika. Evoluce
- NLK Obory
- genetika, lékařská genetika
- experimentální medicína
- NLK Publikační typ
- kolektivní monografie
168 s.
Gene targeting in mice mainly employs homologous recombination (HR) in embryonic stem (ES) cells. Although it is a standard way for production of genetically modified mice, the procedure is laborious and time-consuming. This study describes targeting of the mouse Rosa26 locus by transcription activator-like effector nucleases (TALENs). We employed TALEN-assisted HR in zygotes to introduce constructs encoding TurboRFP and TagBFP fluorescent proteins into the first intron of the Rosa26 gene, and in this way generated two transgenic mice. We also demonstrated that these Rosa26-specific TALENs exhibit high targeting efficiency superior to that of zinc-finger nucleases (ZFNs) specific for the same targeting sequence. Moreover, we devised a reporter assay to assess TALENs activity and specificity to improve the quality of TALEN-assisted targeting.
- MeSH
- endonukleasy metabolismus MeSH
- genetické lokusy genetika MeSH
- genový targeting metody MeSH
- homologní rekombinace MeSH
- myši transgenní MeSH
- myši MeSH
- sekvence nukleotidů MeSH
- zvířata MeSH
- zygota metabolismus MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Methods in molecular biology ; vol. 133
244 s. : il.
- MeSH
- DNA genetika chemie MeSH
- mutace genetika MeSH
- oligonukleotidy genetika chemie MeSH
- oprava DNA imunologie MeSH
- regulace genové exprese imunologie MeSH
- Publikační typ
- přehledy MeSH
The expression of the main cytochrome P450 enzyme CYP3A4 displays enormous interindividual variability. Studies addressing the genetic variability of either the CYP3A4 gene itself or its key transcription factors have not found any crucial polymorphism contributing to this variability in expression, a phenomenon is referred to as the “missing heritability of CYP3A4 variability.” Several reports have recently described microRNAs (miRNAs) targeting the CYP3A4 gene and/or its major transcription factors. A comprehensive bioinformatic analysis was performed using the miRDB, PITA, miRanda and TargetScan programs in the search for hypothetical miRNAs targeting 3′-untranslated regions of PXR, CAR, VDR, HNF4α, RXRα, SHP and GRα genes controlling CYP3A4 expression. We propose several novel miRNAs identified parallelly by at least three algorithms to the target analyzed genes. In particular, we found novel promising miRNAs which may be involved in the indirect PXR-mediated CYP3A4 gene expression such as miR-18a and miR-18b, miR-449a, miR-449b and miR-34a. We also hypothesize that some miRNAs may play the role of a master regulator of NRs since they are predicted to target more than three genes. The identification of miRNAs determining CYP3A4 interindividual variability might be an important step toward progress in pharmacogenetics and personalized medicine.
- Klíčová slova
- jaderné receptory regulující expresi genu CYP3A4,
- MeSH
- biotransformace genetika imunologie účinky léků MeSH
- cytochrom P-450 CYP3A farmakologie genetika účinky léků MeSH
- farmakogenetika metody trendy MeSH
- genetický výzkum MeSH
- individualizovaná medicína metody trendy MeSH
- lidé MeSH
- mikro RNA * farmakologie genetika imunologie MeSH
- regulace genové exprese * genetika imunologie MeSH
- systém (enzymů) cytochromů P-450 genetika účinky léků MeSH
- výpočetní biologie metody trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
