Hai Lan, Szwarc Maria M, Lanza Denise G, Heaney Jason D, Lydon John P
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas.
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas.
Genesis. 2019 Mar;57(3):e23281. doi: 10.1002/dvg.23281. Epub 2019 Jan 23.
The promyelocytic leukemia zinc finger (PLZF) transcription factor mediates a wide-range of biological processes. Accordingly, perturbation of PLZF function results in a myriad of physiologic defects, the most conspicuous of which is abnormal skeletal patterning. Although whole body knockout of Plzf in the mouse (Plzf ) has significantly expanded our understanding of Plzf function in vivo, a conditional knockout mouse model that enables tissue or cell-type specific ablation of Plzf has not been developed. Therefore, we used CRISPR/Cas 9 gene editing to generate a mouse model in which exon 2 of the murine Plzf gene is specifically flanked (or floxed) by LoxP sites (Plzf ). Crossing our Plzf mouse with a global cre-driver mouse to generate the Plzf bigenic mouse, we demonstrate that exon 2 of the Plzf gene is ablated in the Plzf bigenic. Similar to the previously reported Plzf mouse, the Plzf mouse exhibits a severe defect in skeletal patterning of the hindlimb, indicating that the Plzf mouse functions as designed. Therefore, studies in this short technical report demonstrate that the Plzf mouse will be useful to investigators who wish to explore the role of the Plzf transcription factor in a specific tissue or cell-type.
早幼粒细胞白血病锌指（PLZF）转录因子介导多种生物学过程。因此，PLZF功能的紊乱会导致众多生理缺陷，其中最明显的是骨骼模式异常。尽管在小鼠中全身敲除Plzf（Plzf−/−）极大地扩展了我们对Plzf在体内功能的理解，但尚未开发出能实现组织或细胞类型特异性敲除Plzf的条件性敲除小鼠模型。因此，我们利用CRISPR/Cas 9基因编辑技术构建了一个小鼠模型，其中小鼠Plzf基因的外显子2被LoxP位点特异性包围（或称为floxed，即侧翼定位）（Plzffl/fl）。将我们的Plzffl/fl小鼠与全身性cre驱动小鼠杂交以产生Plzf−/−双基因小鼠，我们证明在Plzf−/−双基因小鼠中Plzf基因的外显子2被敲除。与先前报道的Plzf−/−小鼠相似，Plzf−/−小鼠在后肢骨骼模式方面表现出严重缺陷，表明Plzf−/−小鼠按设计发挥作用。因此，本简短技术报告中的研究表明，Plzf−/−小鼠对于希望探索Plzf转录因子在特定组织或细胞类型中作用的研究人员将是有用的。
