RGD Reference Report - Paraoxonase 1 knockout rats have impaired T cell development at the CD4/CD8 double-negative to double-positive transition stage. - Rat Genome Database

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Paraoxonase 1 knockout rats have impaired T cell development at the CD4/CD8 double-negative to double-positive transition stage.

Authors: Bai, Lin  Shi, Guiying  Ma, Yuanwu  Zhang, Li  Guan, Feifei  Zhang, Xu  Xu, Yanfeng  Chen, Houzao  Zhang, Lianfeng 
Citation: Bai L, etal., Sci Rep. 2018 Sep 27;8(1):14457. doi: 10.1038/s41598-018-32780-w.
RGD ID: 45073131
Pubmed: PMID:30262871   (View Abstract at PubMed)
PMCID: PMC6160460   (View Article at PubMed Central)
DOI: DOI:10.1038/s41598-018-32780-w   (Journal Full-text)

Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme that performs multiple physiological activities. Previous studies suggest that PON1 plays an anti-inflammatory role in the cardiovascular system, although its roles in hematopoiesis and adaptive immunity have not been clarified. To investigate the impact of PON1 on the immune system, we generated PON1-knockout (PON1-/-) rats using the CRISPR/Cas9 system. The thymus was smaller in PON1-/- rats than that in wild-type (PON1+/+) rats. Furthermore, analysis of thymocyte development revealed diminished total T cell numbers and a decrease in CD4+, CD8+ and double-positive T cells in peripheral blood and thymus from PON1-/- rats. This may be due to a block in the transition of T cells from the double-negative to the double-positive stage. We also showed that the activation of p38 MAPK phosphorylation contributed to the increased apoptosis and defective T cell development in PON-/- rats. Therefore, our results indicate that PON1 functions as a novel regulator of T cell development.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Pon1Ratarrested T cell differentiation  IMP compared to SDRGD 
Pon1em1LizhRatarrested T cell differentiation  IMP compared to SDRGD 
SD-Pon1em1LizhRatarrested T cell differentiation  IMP compared to SDRGD 
Pon1Ratdecreased B cell number  IMP in spleen and compared to SDRGD 
Pon1em1LizhRatdecreased B cell number  IMP in spleen and compared to SDRGD 
SD-Pon1em1LizhRatdecreased B cell number  IMP in spleen and compared to SDRGD 
Pon1Ratdecreased T cell number  IMP compared to SDRGD 
Pon1em1LizhRatdecreased T cell number  IMP compared to SDRGD 
SD-Pon1em1LizhRatdecreased T cell number  IMP compared to SDRGD 
Pon1Ratdecreased thymocyte number  IMP compared to SDRGD 
Pon1em1LizhRatdecreased thymocyte number  IMP compared to SDRGD 
SD-Pon1em1LizhRatdecreased thymocyte number  IMP compared to SDRGD 
Pon1Ratincreased granulocyte number  IMP in peripheral blood and compared to SDRGD 
Pon1em1LizhRatincreased granulocyte number  IMP in peripheral blood and compared to SDRGD 
SD-Pon1em1LizhRatincreased granulocyte number  IMP in peripheral blood and compared to SDRGD 
Pon1Ratincreased macrophage cell number  IMP in bone marrow and peripheral blood and compared to SDRGD 
Pon1em1LizhRatincreased macrophage cell number  IMP in bone marrow and peripheral blood and compared to SDRGD 
SD-Pon1em1LizhRatincreased macrophage cell number  IMP in bone marrow and peripheral blood and compared to SDRGD 
Pon1Ratincreased T cell apoptosis  IMP compared to SDRGD 
Pon1em1LizhRatincreased T cell apoptosis  IMP compared to SDRGD 
SD-Pon1em1LizhRatincreased T cell apoptosis  IMP compared to SDRGD 
Pon1Ratoxidative stress  IMP compared to SDRGD 
Pon1em1LizhRatoxidative stress  IMP compared to SDRGD 
SD-Pon1em1LizhRatoxidative stress  IMP compared to SDRGD 
Pon1Ratsmall thymus  IMP compared to SDRGD 
Pon1em1LizhRatsmall thymus  IMP compared to SDRGD 
SD-Pon1em1LizhRatsmall thymus  IMP compared to SDRGD 
Objects Annotated

Genes (Rattus norvegicus)
Pon1  (paraoxonase 1)
Pon1em1Lizh  (paraoxonase 1; CRISPR/Cas9 induced mutant 1, Lizh)

Strains
SD-Pon1em1Lizh  (NA)


Additional Information