TY - JOUR
T1 - Generation and comparative analysis of an Itga8-CreER T2 mouse with preferential activity in vascular smooth muscle cells
AU - Warthi, Ganesh
AU - Faulkner, Jessica L.
AU - Doja, Jaser
AU - Ghanam, Amr R.
AU - Gao, Pan
AU - Yang, Allison C.
AU - Slivano, Orazio J.
AU - Barris, Candee T.
AU - Kress, Taylor C.
AU - Zawieja, Scott D.
AU - Griffin, Susan H.
AU - Xie, Xiaoling
AU - Ashworth, Alan
AU - Christie, Christine K.
AU - Bryant, William B.
AU - Kumar, Ajay
AU - Davis, Michael J.
AU - Long, Xiaochun
AU - Gan, Lin
AU - Belin de Chantemèle, Eric J.
AU - Lyu, Qing R.
AU - Miano, Joseph M.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/11
Y1 - 2022/11
N2 - All current smooth muscle cell (SMC) Cre mice similarly recombine floxed alleles in vascular and visceral SMCs. Here we present an Itga8-CreER T2 knock-in mouse and compare its activity with a Myh11-CreER T2 mouse. Both Cre drivers demonstrate equivalent recombination in vascular SMCs. However, Myh11-CreER T2 mice, but not Itga8-CreER T2 mice, display high activity in visceral SMC-containing tissues such as intestine, show early tamoxifen-independent activity and produce high levels of CreERT2 protein. Whereas Myh11-CreER T2-mediated knockout of serum response factor (Srf) causes a lethal intestinal phenotype precluding analysis of the vasculature, loss of Srf with Itga8-CreER T2 (Srf Itga8) yields viable mice with no evidence of intestinal pathology. Male and female Srf Itga8 mice exhibit vascular contractile incompetence, and angiotensin II causes elevated blood pressure in wild-type, but not Srf Itga8, male mice. These findings establish the Itga8-CreER T2 mouse as an alternative to existing SMC Cre mice for unfettered phenotyping of vascular SMCs after selective gene loss.
AB - All current smooth muscle cell (SMC) Cre mice similarly recombine floxed alleles in vascular and visceral SMCs. Here we present an Itga8-CreER T2 knock-in mouse and compare its activity with a Myh11-CreER T2 mouse. Both Cre drivers demonstrate equivalent recombination in vascular SMCs. However, Myh11-CreER T2 mice, but not Itga8-CreER T2 mice, display high activity in visceral SMC-containing tissues such as intestine, show early tamoxifen-independent activity and produce high levels of CreERT2 protein. Whereas Myh11-CreER T2-mediated knockout of serum response factor (Srf) causes a lethal intestinal phenotype precluding analysis of the vasculature, loss of Srf with Itga8-CreER T2 (Srf Itga8) yields viable mice with no evidence of intestinal pathology. Male and female Srf Itga8 mice exhibit vascular contractile incompetence, and angiotensin II causes elevated blood pressure in wild-type, but not Srf Itga8, male mice. These findings establish the Itga8-CreER T2 mouse as an alternative to existing SMC Cre mice for unfettered phenotyping of vascular SMCs after selective gene loss.
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U2 - 10.1038/s44161-022-00162-1
DO - 10.1038/s44161-022-00162-1
M3 - Article
AN - SCOPUS:85146753406
SN - 2731-0590
VL - 1
SP - 1084
EP - 1100
JO - Nature Cardiovascular Research
JF - Nature Cardiovascular Research
IS - 11
ER -