造血干细胞S100A8特异性敲除鼠表型分析及对红系前体细胞发育的影响

Phenotype analysis of hematopoietic stem cell S100A8 knockout mice and the effect of S100A8 knockout on erythroid development

目的通过构建造血干细胞S100A8基因特异性敲除鼠,对其表型进行初步研究,并分析其对红系前体细胞发育的影响。方法利用CRISPR/Cas9基因编辑技术构建造血干细胞S100A8基因特异性敲除鼠;观察分析子代鼠大小便、毛发、体质量、性别比例及细胞形态等生长发育情况;构建荷瘤和贫血模型,分析红系前体细胞变化发育情况。结果成功构建了造血干细胞S100A8基因敲除鼠,该鼠可生长发育繁殖,小鼠偶会现脱毛现象,8周龄前体质量低于野生型鼠;荷瘤及贫血模型中,红系前体细胞比例变化趋势相似;白细胞及其亚群数量未见明显统计学差异。结论首次成功构建了造血干细胞S100A8基因敲除鼠,为研究其功能提供了新的模型;该基因特异性敲除会影响小鼠早期表型,但不会对红系前体细胞发育产生影响。

It is known that anemia often occurs in patients with advanced cancer,and S100A8 may participate this process.This study was designed to construct a mouse model of conditional hematopoietic stem cell S100A8 gene KO by the CRISPR/Cas9,and to evaluate the phenotype of the mice and the influence on erythroid development.By observing and analyzing the general phenotype of the mice,conditional S100A8 KO appeared to affect the early phenotype of the mice.Furthermore,a tumor model and an anemia model were constructed to study the hematopoietic ability.No significant differences were found in tumor microenvironment and the result indicated acceptably rapid hematopoietic recovery ability in face of acute hemolytic anemia.Therefore,conditional S100A8 KO showed no effect on erythroid development.This study enriches the knowledge of S100A8 and provides new understanding and ideas for further research.