The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis.
The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis.
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DOI：
10.1084/jem.20100147
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发表时间：
2010-07-05
期刊：
影响因子：
--
通讯作者：
Colgan JD
中科院分区：
文献类型：
--
作者：
Lu P;Hankel IL;Knisz J;Marquardt A;Chiang MY;Grosse J;Constien R;Meyer T;Schroeder A;Zeitlmann L;Al-Alem U;Friedman AD;Elliott EI;Meyerholz DK;Waldschmidt TJ;Rothman PB;Colgan JD
一种名为Justy的隐性突变被发现可以消除B淋巴细胞生成，但不损害造血的其他主要方面。移植实验表明，纯合性Justy阻止造血祖细胞产生B细胞，但不影响骨髓基质支持B淋巴细胞生成的能力。在突变小鼠的骨髓中，常见的淋巴祖细胞和前原B细胞似乎正常，但在随后阶段的B淋巴细胞生成的细胞数量显着减少。在促进B淋巴细胞生成的培养条件下，突变的前原B细胞保持存活，并开始表达B细胞标记物CD 19，但不能增殖。相反，这些细胞能够产生髓样或T/NK前体。遗传和分子分析表明，Justy是Gon 4样（Gon 4l）基因内的一个点突变，该基因编码一种与转录调节因子同源的蛋白质。发现该突变破坏Gon 4l前mRNA剪接并显著降低野生型Gon 4l RNA和蛋白质的表达。与Gon 4l在转录调控中的作用一致，编码C/EBPα和PU. 1的RNA水平在突变型B祖细胞中异常高。我们的研究结果表明，Gon 4l蛋白是B淋巴细胞生成所需的，并可能在此过程中发挥调节基因表达的作用。
A recessive mutation named Justy was found that abolishes B lymphopoiesis but does not impair other major aspects of hematopoiesis. Transplantation experiments showed that homozygosity for Justy prevented hematopoietic progenitors from generating B cells but did not affect the ability of bone marrow stroma to support B lymphopoiesis. In bone marrow from mutant mice, common lymphoid progenitors and pre-pro–B cells appeared normal, but cells at subsequent stages of B lymphopoiesis were dramatically reduced in number. Under culture conditions that promoted B lymphopoiesis, mutant pre-pro–B cells remained alive and began expressing the B cell marker CD19 but failed to proliferate. In contrast, these cells were able to generate myeloid or T/NK precursors. Genetic and molecular analysis demonstrated that Justy is a point mutation within the Gon4-like (Gon4l) gene, which encodes a protein with homology to transcriptional regulators. This mutation was found to disrupt Gon4l pre-mRNA splicing and dramatically reduce expression of wild-type Gon4l RNA and protein. Consistent with a role for Gon4l in transcriptional regulation, the levels of RNA encoding C/EBPα and PU.1 were abnormally high in mutant B cell progenitors. Our findings indicate that the Gon4l protein is required for B lymphopoiesis and may function to regulate gene expression during this process.
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DOI：
10.1016/j.bbagrm.2009.05.007
发表时间：
2009-06
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Grzenda A;Lomberk G;Zhang JS;Urrutia R
通讯作者：
Urrutia R
影响因子：
20.3
作者：
Mansson, Robert;Zandi, Sasan;Sigvardsson, Mikael
通讯作者：
Sigvardsson, Mikael
影响因子：
5.4
作者：
Balciunaite, G;Ceredig, R;Rolink, AG
通讯作者：
Rolink, AG
影响因子：
10.5
作者：
Inlay, Matthew A.;Bhattacharya, Deepta;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
11.4
作者：
Eberhard, D;Jiménez, G;Busslinger, M
通讯作者：
Busslinger, M