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Gene Targeting Reveals a Crucial Role forMTG8 in the Gut

机译:基因靶向揭示了肠道中MTG8的关键作用

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The MTG8 (ETO) locus is involved in a reciprocal exchange with runx1 in the t(8;21) of acute myeloid leukemia. It is a member of a small gene family encoding transcriptional regulators that interact with corepressors and histone deacetylase. However, the physiologic cellular processes controlled byMTG8 are not known. In order to gain an insight into the latter, we have generated mutant mice with an insertional inactivation at the locus, which disrupts transcription of exon 2. The postnatal viability of homozygous mutants was greatly reduced. In approximately 25% the midgut was missing, whereas practically all pups surviving past the first 2 days showed severe growth impairment, which was likely due to a gross disruption of the gut architecture. The latter phenotype could be traced back to late embryonic development. No difference in gut cell differentiation or proliferation was found compared to wild-type littermates. Levels of factors known to be involved in gut morphogenesis were also unchanged. MTG8 is expressed in the outermost layers of the developing gut from at least E9.5. Thus,MTG8 plays a novel, essential role in the gastrointestinal system.
机译:在急性髓细胞白血病的t(8; 21)中, MTG8 ETO )基因座与 runx1 相互交换。它是一个小基因家族的成员,该家族编码与核心加压因子和组蛋白脱乙酰基酶相互作用的转录调节因子。但是,由 MTG8 控制的生理细胞过程尚不清楚。为了深入了解后者,我们生成了在位点具有插入失活的突变小鼠,这会破坏外显子2的转录。纯合突变体的出生后生存能力大大降低。大约有25%的中肠失踪,而几乎所有存活的超过头2天的幼崽都表现出严重的生长障碍,这很可能是由于肠道结构的彻底破坏所致。后者的表型可以追溯到晚期胚胎发育。与野生型同窝仔相比,未发现肠道细胞分化或增殖的差异。已知与肠道形态发生有关的因子水平也未改变。 MTG8 在至少E9.5的发育肠最外层表达。因此, MTG8 在胃肠道系统中起着新的重要作用。

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