Zheng Xi, Wang Fengjiao, Hu Xiaoxiao, Li Hua, Guan Zhen, Zhang Yanding, Hu Xuefeng
Fujian Key Laboratory of Developmental and Neural Biology & Southern Center for Biomedical Research, College of Life Sciences, Fujian Normal University, Fuzhou, China.
Key Laboratory of Stem Cell Engineering Societ and Regenerative Medicine, School of Basic Medical Science, Fujian Medical University, Fuzhou, China.
Front Cell Dev Biol. 2021 Jun 10;9:647165. doi: 10.3389/fcell.2021.647165. eCollection 2021.
Palate-derived growth factor receptor α (Pdgfrα) signaling has been reported to play important roles in the cardiac development. A previous study utilizing conventional knockout mice reported hypoplasia of the sinus venous myocardium including the sinoatrial node (SAN) accompanied by increased expression of Nkx2.5. This mouse line embryos die by E11.5 due to embryonic lethality, rendering them difficult to investigate the details. To elucidate the underlying mechanism, in this study, we revisited this observation by generation of specific ablation of in the SAN by Shox2-Cre at E9.5, using a -; conditional mouse line. Surprisingly, we found that resultant homozygous mutant mice did not exhibit any malformation in SAN morphology as compared to their wild-type littermates. Further analysis revealed the normal cardiac function in adult mutant mice assessed by the record of heart rate and electrocardiogram and unaltered expression of Nkx2.5 in the E13.5 SAN of conditional knockout mice. Our results unambiguously demonstrate that is dispensable for SAN development after its fate commitment in mice.
据报道,腭源生长因子受体α(Pdgfrα)信号通路在心脏发育中发挥重要作用。先前一项利用传统基因敲除小鼠的研究报告称,包括窦房结(SAN)在内的静脉窦心肌发育不全,同时伴有Nkx2.5表达增加。该品系小鼠胚胎在E11.5时因胚胎致死而死亡,这使得难以研究其详细情况。为了阐明潜在机制,在本研究中,我们通过在E9.5时利用Shox2-Cre在窦房结中特异性敲除,使用一种条件性小鼠品系,重新审视了这一观察结果。令人惊讶的是,我们发现与野生型同窝小鼠相比,产生的纯合突变小鼠在窦房结形态上没有表现出任何畸形。进一步分析显示,通过心率和心电图记录评估,成年突变小鼠心脏功能正常,且条件性敲除小鼠E13.5窦房结中Nkx2.5表达未改变。我们的结果明确表明,在小鼠中,在其命运确定后,窦房结发育中该基因是可有可无的。