Defects of protein production in erythroid cells revealed in a zebrafish   Diamond-Blackfan anemia model for mutation in RPS19

doi:10.1038/cddis.2014.318

CORC > 北京大学 > 生命科学学院

	Defects of protein production in erythroid cells revealed in a zebrafish Diamond-Blackfan anemia model for mutation in RPS19
	Zhang, Y. ; Ear, J. ; Yang, Z. ; Morimoto, K. ; Zhang, B. ; Lin, S.
刊名	cell death disease
	2014
关键词	L-LEUCINE IMPROVES 18S RIBOSOMAL-RNA MESSENGER-RNA S19 DEFICIENCY GENE TRANSLATION EXPRESSION L11 ERYTHROPOIESIS ABNORMALITIES
DOI	10.1038/cddis.2014.318
英文摘要	Diamond-Blackfan anemia (DBA) is a rare congenital red cell aplasia that classically presents during early infancy in DBA patients. Approximately, 25% of patients carry a mutation in the ribosomal protein (RP) S19 gene; mutations in RPS24, RPS17, RPL35A, RPL11, and RPL5 have been reported. How ribosome protein deficiency causes defects specifically to red blood cells in DBA has not been well elucidated. To genetically model the predominant ribosome defect in DBA, we generated an rps19 null mutant through the use of TALEN-mediated gene targeting in zebrafish. Molecular characterization of this mutant line demonstrated that rps19 deficiency reproduced the erythroid defects of DBA, including a lack of mature red blood cells and p53 activation. Notably, we found that rps19 mutants' production of globin proteins was significantly inhibited; however, globin transcript level was either increased or unaffected in rps19 mutant embryos. This dissociation of RNA/protein levels of globin genes was confirmed in another zebrafish DBA model with defects in rpl11. Using transgenic zebrafish with specific expression of mCherry in erythroid cells, we showed that protein production in erythroid cells was decreased when either rps19 or rpl11 was mutated. L-Leucine treatment alleviated the defects of protein production in erythroid cells and partially rescued the anemic phenotype in both rps19 and rpl11 mutants. Analysis of this model suggests that the decreased protein production in erythroid cells likely contributes to the blood-specific phenotype of DBA. Furthermore, the newly generated rps19 zebrafish mutant should serve as a useful animal model to study DBA. Our in vivo findings may provide clues for the future therapy strategy for DBA.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341639300043&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Cell Biology; SCI(E); PubMed; 9; ARTICLE; shuolin@ucla.edu; e1352; 5
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/162435]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhang, Y.,Ear, J.,Yang, Z.,et al. Defects of protein production in erythroid cells revealed in a zebrafish Diamond-Blackfan anemia model for mutation in RPS19[J]. cell death disease,2014.
APA	Zhang, Y.,Ear, J.,Yang, Z.,Morimoto, K.,Zhang, B.,&Lin, S..(2014).Defects of protein production in erythroid cells revealed in a zebrafish Diamond-Blackfan anemia model for mutation in RPS19.cell death disease.
MLA	Zhang, Y.,et al."Defects of protein production in erythroid cells revealed in a zebrafish Diamond-Blackfan anemia model for mutation in RPS19".cell death disease (2014).