-
Je něco špatně v tomto záznamu ?
Targeting of the Plzf Gene in the Rat by Transcription Activator-Like Effector Nuclease Results in Caudal Regression Syndrome in Spontaneously Hypertensive Rats
F. Liška, R. Peterková, M. Peterka, V. Landa, V. Zídek, P. Mlejnek, J. Šilhavý, M. Šimáková, V. Křen, CG. Starker, DF. Voytas, Z. Izsvák, M. Pravenec,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Free Medical Journals od 2006
Public Library of Science (PLoS) od 2006
PubMed Central od 2006
Europe PubMed Central od 2006
ProQuest Central od 2006-12-01
Open Access Digital Library od 2006-10-01
Open Access Digital Library od 2006-01-01
Open Access Digital Library od 2006-01-01
Medline Complete (EBSCOhost) od 2008-01-01
Nursing & Allied Health Database (ProQuest) od 2006-12-01
Health & Medicine (ProQuest) od 2006-12-01
Public Health Database (ProQuest) od 2006-12-01
ROAD: Directory of Open Access Scholarly Resources od 2006
Odkazy
PubMed
27727328
DOI
10.1371/journal.pone.0164206
Knihovny.cz E-zdroje
- MeSH
- alely MeSH
- DNA vazebné proteiny nedostatek genetika metabolismus MeSH
- exony MeSH
- genotyp MeSH
- genový targeting MeSH
- heterozygot MeSH
- homozygot MeSH
- krysa rodu rattus MeSH
- lokus kvantitativního znaku MeSH
- mnohočetné abnormality genetika patologie veterinární MeSH
- ocas abnormality MeSH
- polydaktylie genetika patologie veterinární MeSH
- posunová mutace MeSH
- potkani inbrední SHR MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- TALENs genetika metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Recently, it has been found that spontaneous mutation Lx (polydactyly-luxate syndrome) in the rat is determined by deletion of a conserved intronic sequence of the Plzf (Promyelocytic leukemia zinc finger protein) gene. In addition, Plzf is a prominent candidate gene for quantitative trait loci (QTLs) associated with cardiac hypertrophy and fibrosis in the spontaneously hypertensive rat (SHR). In the current study, we tested the effects of Plzf gene targeting in the SHR using TALENs (transcription activator-like effector nucleases). SHR ova were microinjected with constructs pTAL438/439 coding for a sequence-specific endonuclease that binds to target sequence in the first coding exon of the Plzf gene. Out of 43 animals born after microinjection, we detected a single male founder. Sequence analysis revealed a deletion of G that resulted in frame shift mutation starting in codon 31 and causing a premature stop codon at position of amino acid 58. The Plzftm1Ipcv allele is semi-lethal since approximately 95% of newborn homozygous animals died perinatally. All homozygous animals exhibited manifestations of a caudal regression syndrome including tail anomalies and serious size reduction and deformities of long bones, and oligo- or polydactyly on the hindlimbs. The heterozygous animals only exhibited the tail anomalies. Impaired development of the urinary tract was also revealed: one homozygous and one heterozygous rat exhibited a vesico-ureteric reflux with enormous dilatation of ureters and renal pelvis. In the homozygote, this was combined with a hypoplastic kidney. These results provide evidence for the important role of Plzf gene during development of the caudal part of a body-column vertebrae, hindlimbs and urinary system in the rat.
Institute of Experimental Medicine Czech Academy of Sciences Prague Czech Republic
Institute of Physiology Czech Academy of Sciences Prague Czech Republic
Max Delbrück Center for Molecular Medicine Berlin Germany
University of Minnesota Minneapolis Minnesota United States of America
- 000
- 00000naa a2200000 a 4500
- 001
- bmc17023643
- 003
- CZ-PrNML
- 005
- 20170720122309.0
- 007
- ta
- 008
- 170720s2016 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1371/journal.pone.0164206 $2 doi
- 035 __
- $a (PubMed)27727328
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Liška, František $u Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University in Prague, Prague, Czech Republic.
- 245 10
- $a Targeting of the Plzf Gene in the Rat by Transcription Activator-Like Effector Nuclease Results in Caudal Regression Syndrome in Spontaneously Hypertensive Rats / $c F. Liška, R. Peterková, M. Peterka, V. Landa, V. Zídek, P. Mlejnek, J. Šilhavý, M. Šimáková, V. Křen, CG. Starker, DF. Voytas, Z. Izsvák, M. Pravenec,
- 520 9_
- $a Recently, it has been found that spontaneous mutation Lx (polydactyly-luxate syndrome) in the rat is determined by deletion of a conserved intronic sequence of the Plzf (Promyelocytic leukemia zinc finger protein) gene. In addition, Plzf is a prominent candidate gene for quantitative trait loci (QTLs) associated with cardiac hypertrophy and fibrosis in the spontaneously hypertensive rat (SHR). In the current study, we tested the effects of Plzf gene targeting in the SHR using TALENs (transcription activator-like effector nucleases). SHR ova were microinjected with constructs pTAL438/439 coding for a sequence-specific endonuclease that binds to target sequence in the first coding exon of the Plzf gene. Out of 43 animals born after microinjection, we detected a single male founder. Sequence analysis revealed a deletion of G that resulted in frame shift mutation starting in codon 31 and causing a premature stop codon at position of amino acid 58. The Plzftm1Ipcv allele is semi-lethal since approximately 95% of newborn homozygous animals died perinatally. All homozygous animals exhibited manifestations of a caudal regression syndrome including tail anomalies and serious size reduction and deformities of long bones, and oligo- or polydactyly on the hindlimbs. The heterozygous animals only exhibited the tail anomalies. Impaired development of the urinary tract was also revealed: one homozygous and one heterozygous rat exhibited a vesico-ureteric reflux with enormous dilatation of ureters and renal pelvis. In the homozygote, this was combined with a hypoplastic kidney. These results provide evidence for the important role of Plzf gene during development of the caudal part of a body-column vertebrae, hindlimbs and urinary system in the rat.
- 650 _2
- $a mnohočetné abnormality $x genetika $x patologie $x veterinární $7 D000015
- 650 _2
- $a alely $7 D000483
- 650 _2
- $a sekvence aminokyselin $7 D000595
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a sekvence nukleotidů $7 D001483
- 650 _2
- $a DNA vazebné proteiny $x nedostatek $x genetika $x metabolismus $7 D004268
- 650 _2
- $a exony $7 D005091
- 650 _2
- $a posunová mutace $7 D016368
- 650 _2
- $a genový targeting $7 D018390
- 650 _2
- $a genotyp $7 D005838
- 650 _2
- $a heterozygot $7 D006579
- 650 _2
- $a homozygot $7 D006720
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a polydaktylie $x genetika $x patologie $x veterinární $7 D017689
- 650 _2
- $a vazba proteinů $7 D011485
- 650 _2
- $a lokus kvantitativního znaku $7 D040641
- 650 _2
- $a krysa rodu Rattus $7 D051381
- 650 _2
- $a potkani inbrední SHR $7 D011918
- 650 _2
- $a ocas $x abnormality $7 D013623
- 650 _2
- $a TALENs $x genetika $x metabolismus $7 D000069896
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Peterková, Renata $u Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Peterka, Miroslav $u Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Landa, Vladimír $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Zídek, Václav $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Mlejnek, Petr $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Šilhavý, Jan $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Šimáková, Miroslava $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Křen, Vladimír $u Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University in Prague, Prague, Czech Republic. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Starker, Colby G $u University of Minnesota, Minneapolis, Minnesota, United States of America.
- 700 1_
- $a Voytas, Daniel F $u University of Minnesota, Minneapolis, Minnesota, United States of America.
- 700 1_
- $a Izsvák, Zsuzsanna $u Max Delbrück Center for Molecular Medicine, Berlin, Germany.
- 700 1_
- $a Pravenec, Michal $u Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University in Prague, Prague, Czech Republic. Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.
- 773 0_
- $w MED00180950 $t PloS one $x 1932-6203 $g Roč. 11, č. 10 (2016), s. e0164206
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/27727328 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20170720 $b ABA008
- 991 __
- $a 20170720122802 $b ABA008
- 999 __
- $a ok $b bmc $g 1239324 $s 984556
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2016 $b 11 $c 10 $d e0164206 $e 20161011 $i 1932-6203 $m PLoS One $n PLoS One $x MED00180950
- LZP __
- $a Pubmed-20170720