Warthi Ganesh, Faulkner Jessica L, Doja Jaser, Ghanam Amr R, Gao Pan, Yang Allison C, Slivano Orazio J, Barris Candee T, Kress Taylor C, Zawieja Scott D, Griffin Susan H, Xie Xiaoling, Ashworth Alan, Christie Christine K, Bryant William B, Kumar Ajay, Davis Michael J, Long Xiaochun, Gan Lin, Belin de Chantemele Eric J, Lyu Qing, Miano Joseph M
Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia 30912.
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia 30912.
Nat Cardiovasc Res. 2022 Nov;1(11):1084-1100. doi: 10.1038/s44161-022-00162-1. Epub 2022 Nov 11.
All current smooth muscle cell (SMC) mice similarly recombine floxed alleles in vascular and visceral SMCs. Here, we present an knock-in mouse and compare its activity with a mouse. Both drivers demonstrate equivalent recombination in vascular SMCs. However, mice, but not mice, display high activity in visceral SMC-containing tissues such as intestine, show early tamoxifen-independent activity, and produce high levels of CreER protein. Whereas -mediated knockout of serum response factor () causes a lethal intestinal phenotype precluding analysis of the vasculature, loss of with ( ) yields viable mice with no evidence of intestinal pathology. Male and female mice exhibit vascular contractile incompetence, and angiotensin II causes elevated blood pressure in wild type, but not , male mice. These findings establish the mouse as an alternative to existing SMC mice for unfettered phenotyping of vascular SMCs following selective gene loss.
所有当前的平滑肌细胞(SMC)小鼠在血管和内脏平滑肌细胞中类似地重组了floxed等位基因。在此,我们展示了一种敲入小鼠,并将其活性与一种[未提及具体名称的]小鼠进行比较。两种驱动小鼠在血管平滑肌细胞中表现出等效的重组。然而,[未提及具体名称的]小鼠(而非[另一种未提及具体名称的]小鼠)在内脏含平滑肌细胞的组织(如肠道)中表现出高活性,显示出早期他莫昔芬非依赖性活性,并产生高水平的CreER蛋白。虽然[未提及具体名称的]介导的血清反应因子(SRF)敲除导致致命的肠道表型,排除了对脉管系统的分析,但使用[未提及具体名称的]([具体名称])敲除SRF可产生存活的小鼠,且无肠道病理学证据。雄性和雌性[未提及具体名称的]小鼠表现出血管收缩功能不全,并且血管紧张素II在野生型雄性小鼠中导致血压升高,但在[未提及具体名称的]雄性小鼠中则不然。这些发现确立了[未提及具体名称的]小鼠作为现有SMC[未提及具体名称的]小鼠的替代物,用于在选择性基因缺失后对血管平滑肌细胞进行不受限制的表型分析。