Truncation of the MLL gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos
Truncation of the MLL gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos
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DOI：
10.1002/gene.1066
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发表时间：
2001-08-01
期刊：
影响因子：
1.5
通讯作者：
Subramanian, V
中科院分区：
文献类型：
--
作者：
Ayton, P;Sneddon, SF;Subramanian, V
混合谱系白血病基因（MLL）最初是通过其参与白血病的相互易位而被发现的。 MLL 编码一个大的多结构域蛋白，并且在氨基末端区域的两个小结构域、中央锌指结构域和羧基SET结构域中与果蝇发育控制基因trithorax具有同源性。与果蝇 trx 一样，MLL 也被证明是 Hox 基因表达的正调节因子。我们以外显子 5 中的 MII（MLL 的鼠同源物）为目标，导致三个截短的框内 MII 转录本的表达。这些转录物保留全部或部分 AT 钩基序和 DMT 结构域。该突变等位基因导致纯合胚胎在 2 细胞阶段之前早期体内植入前致死。体外培养的胚胎进展到2细胞阶段，但进一步发育受到抑制。杂合子表现出轻度骨骼缺陷以及一些神经外胚层衍生物的缺陷。 (C) 2001 Wiley-Liss, Inc.
The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted MII (the murine homologue of MLL) in exon 5 causing expression of three truncated in-frame MII transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2-cell stage. Embryos cultured in vitro progress to the 2-cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives. (C) 2001 Wiley-Liss, Inc.