Souroullas George P, Goodell Margaret A
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Genesis. 2011 Jun;49(6):441-8. doi: 10.1002/dvg.20743. Epub 2011 May 31.
Lyl1 codes for a bHLH protein that is an important regulator of hematopoietic stem cell function. An existing mutant allele of Lyl1 features a lacZ gene inserted in-frame into the fourth exon, leaving behind the N-terminus and the DNA-binding basic region, resulting in a translated chimeric protein. Here, we have generated a null allele, which allowed us to examine residual function of the N-terminus in the absence of a bHLH region. The new Lyl1-/- mouse model exhibited a reduced ability to generate lymphoid lineages and a somewhat more severe hematopoietic repopulation defect when transplanting purified hematopoietic stem cells. Our data show that in the absence of the HLH but presence of the N-terminus, residual function of the Lyl1 is detectable but relatively minor. The new model may be of use for studies of Lyl1 in which a null allele is required, or for which presence of the LacZ may complicate the combined use of additional mouse models bearing the lacZ marker.
Lyl1编码一种bHLH蛋白，它是造血干细胞功能的重要调节因子。Lyl1的一个现有突变等位基因的特征是，一个lacZ基因框内插入到第四外显子中，留下N端和DNA结合碱性区域，导致翻译出嵌合蛋白。在这里，我们产生了一个无效等位基因，这使我们能够在没有bHLH区域的情况下检查N端的残余功能。当移植纯化的造血干细胞时，新的Lyl1-/-小鼠模型产生淋巴谱系的能力降低，造血重建缺陷更为严重。我们的数据表明，在没有HLH但有N端的情况下，Lyl1的残余功能是可检测到的，但相对较小。新模型可用于需要无效等位基因的Lyl1研究，或用于LacZ的存在可能使携带lacZ标记的其他小鼠模型联合使用复杂化的研究。
