Targeted disruption of the ribosomal protein S19 gene is lethal prior to implantation
Targeted disruption of the ribosomal protein S19 gene is lethal prior to implantation
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DOI：
10.1128/mcb.24.9.4032-4037.2004
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Dahl, N
中科院分区：
文献类型：
--
作者：
Matsson, H;Davey, EJ;Dahl, N
核糖体蛋白S19（RPS 19）位于核糖体小（40 S）亚基中，是79种核糖体蛋白之一。编码RPS 19的基因在大约25%的Diamond-Blackfan贫血患者中发生突变，Diamond-Blackfan贫血是一种罕见的先天性成红细胞减少症。受影响的个体表现为骨髓中红系前体细胞数量减少或缺乏，并且各种器官的相关畸形是常见的。我们产生了C57 BL/6 J小鼠与鼠Rps 19的靶向破坏，以研究其在红细胞生成和发育中的作用。早在胚泡阶段就没有鉴定出Rps 19破坏的纯合子小鼠，表明其具有致死作用。相反，Rps 19等位基因杂合的小鼠具有正常的生长和器官发育，包括造血系统。我们的研究结果表明，Rps 19（-/-）的受精卵不形成囊胚，而一个正常的Rps 19等位基因在C57 BL/6 J小鼠足以维持正常的核糖体和可能的核糖体外功能。
The ribosomal protein S19 (RPS19) is located in the small (40S) subunit and is one of 79 ribosomal proteins. The gene encoding RPS19 is mutated in approximately 25% of patients with Diamond-Blackfan anemia, which is a rare congenital erythroblastopenia. Affected individuals present with decreased numbers or the absence of erythroid precursors in the bone marrow, and associated malformations of various organs are common. We produced C57BL/6J mice with a targeted disruption of murine Rps19 to study its role in erythropoiesis and development. Mice homozygous for the disrupted Rps19 were not identified as early as the blastocyst stage, indicating a lethal effect. In contrast, mice heterozygous for the disrupted Rps19 allele have normal growth and organ development, including that of the hematopoietic system. Our findings indicate that zygotes which are Rps19(-/-) do not form blastocysts, whereas one normal Rps19 allele in C57BL/6J mice is sufficient to maintain normal ribosomal and possibly extraribosomal functions.