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首页> 外文期刊>Molecular and Cellular Biology >Myeloid expression of the human c-fps/fes proto-oncogene in transgenic mice.
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Myeloid expression of the human c-fps/fes proto-oncogene in transgenic mice.

机译：人类c-fps / fes原癌基因在转基因小鼠中的骨髓表达。

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The mammalian c-fps/fes proto-oncogene encodes a 92-kilodalton cytoplasmic protein-tyrosine kinase (p92c-fes), which is expressed in immature and differentiated hematopoietic cells of the myeloid lineage. To determine the limits of the c-fps/fes locus and to investigate the cis-acting sequences required to direct appropriate tissue-specific expression, a 13-kilobase-pair fragment of human genomic DNA containing the entire c-fps/fes coding sequence was introduced into the mouse germ line. Transcription of the human c-fps/fes transgene was highest in bone marrow and showed a tissue distribution identical to that of the endogenous mouse gene. Macrophages cultured from transgenic mouse bone marrow contained particularly high levels of human and murine c-fps/fes RNA. Furthermore, expression of human c-fps/fes RNA induced a proportionate increase in the level of the p92c-fes protein-tyrosine kinase in bone marrow, bone marrow-derived macrophages, and spleen. Elevated levels of normal human p92c-fes had no obvious effect on mouse development or hematopoiesis. Remarkably, given the short 5'- and 3'-flanking sequences, expression of the human proto-oncogene in bone marrow was independent of integration site, was proportional to the transgene copy number, and was of comparable efficiency to that of the endogenous mouse c-fps/fes gene. The 13-kilobase-pair fragment therefore defines a genetic locus sufficient for the appropriate tissue-specific expression of the fps/fes protein-tyrosine kinase and includes a dominant cis-acting element that directs integration-independent myeloid expression in transgenic mice.
机译：哺乳动物的c-fps / fes原癌基因编码一个92千达尔顿的细胞质蛋白酪氨酸激酶（p92c-fes），它在骨髓谱系的未成熟和分化的造血细胞中表达。为了确定c-fps / fes基因座的限度并研究指导适当的组织特异性表达所需的顺式作用序列，人类基因组DNA的13碱基对片段包含完整的c-fps / fes编码序列被引入小鼠种系。人c-fps / fes转基因的转录在骨髓中最高，并且显示出与内源小鼠基因相同的组织分布。从转基因小鼠骨髓培养的巨噬细胞含有特别高水平的人和鼠c-fps / fes RNA。此外，人c-fps / fes RNA的表达在骨髓，骨髓源性巨噬细胞和脾脏中引起p92c-fes蛋白-酪氨酸激酶水平的相应增加。正常人p92c-fes水平升高对小鼠发育或造血没有明显影响。值得注意的是，考虑到短的5'-和3'-侧翼序列，人原癌基因在骨髓中的表达与整合位点无关，与转基因拷贝数成正比，并且具有与内源小鼠相当的效率c-fps / fes基因。因此，13碱基对片段定义了足以用于fps / fes蛋白-酪氨酸激酶的组织特异性表达的遗传位点，并包括一个主要的顺式作用元件，该元件指导转基因小鼠中非整合性髓样表达。

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