RGD Reference Report - Targeting of the Plzf Gene in the Rat by Transcription Activator-Like Effector Nuclease Results in Caudal Regression Syndrome in Spontaneously Hypertensive Rats. - Rat Genome Database

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Targeting of the Plzf Gene in the Rat by Transcription Activator-Like Effector Nuclease Results in Caudal Regression Syndrome in Spontaneously Hypertensive Rats.

Authors: Liška, František  Peterková, Renata  Peterka, Miroslav  Landa, Vladimír  Zídek, Václav  Mlejnek, Petr  Šilhavý, Jan  Šimáková, Miroslava  Křen, Vladimír  Starker, Colby G  Voytas, Daniel F  Izsvák, Zsuzsanna  Pravenec, Michal 
Citation: Liška F, etal., PLoS One. 2016 Oct 11;11(10):e0164206. doi: 10.1371/journal.pone.0164206. eCollection 2016.
RGD ID: 40924666
Pubmed: PMID:27727328   (View Abstract at PubMed)
PMCID: PMC5058558   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0164206   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ZBTB16Humancaudal regression syndrome  ISOZbtb16 (Rattus norvegicus) RGD 
Zbtb16Ratcaudal regression syndrome  IAGP  RGD 
Zbtb16Mousecaudal regression syndrome  ISOZbtb16 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Zbtb16Ratossification involved in bone maturation  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Zbtb16Ratabnormal ossification involved in bone maturation  IAGP  RGD 
Zbtb16Ratabnormal tail development  IAGP  RGD 
Zbtb16Ratdecreased fetal weight  IAGP  RGD 
Zbtb16Ratdecreased length of long bones  IAGP  RGD 
Zbtb16Ratembryonic lethality, incomplete penetrance  IAGP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Zbtb16  (zinc finger and BTB domain containing 16)

Genes (Mus musculus)
Zbtb16  (zinc finger and BTB domain containing 16)

Genes (Homo sapiens)
ZBTB16  (zinc finger and BTB domain containing 16)


Additional Information