New Autosomal
 Myh11-CreER
 
 T
 2
 
 Smooth Muscle Cell Lineage Tracing and Gene Knockout Mouse Model


 
 
 The
 Myh11
 promoter is extensively used as a smooth muscle cell (SMC) Cre-driver and is regarded as the most restrictive and specific promoter available to study SMCs. Unfortunately, in the existing
 Myh11-CreER
 
 T
 2
 
 mouse, the transgene was inserted on the Y chromosome precluding the study of female mice. Given the importance of including sex as a biological variable and that numerous SMC-based diseases have a sex-dependent bias, the field has been tremendously limited by the lack of a model to study both sexes. Here, we describe a new autosomal
 Myh11-CreER
 
 T
 2
 
 mouse (referred to as
 Myh11-CreER
 
 T
 2
 
 -RAD
 ), which allows for SMC-specific lineage tracing and gene knockout studies in vivo using both male and female mice.
 
 
 
 
 
 A
 Myh11-CreER
 
 T
 2
 
 -RAD
 transgenic C57BL/6 mouse line was generated using bacterial artificial chromosome clone RP23-151J22 modified to contain a
 Cre-ER
 
 T
 2
 
 after the
 Myh11
 start codon.
 Myh11-CreER
 
 T
 2
 
 -RAD
 mice were crossed with 2 different fluorescent reporter mice and tested for SMC-specific labeling by flow cytometric and immunofluorescence analyses.
 
 
 
 
 
 Myh11-CreER
 
 T
 2
 
 -RAD
 transgene insertion was determined to be on mouse chromosome 2.
 Myh11-CreER
 
 T
 2
 
 -RAD
 fluorescent reporter mice showed Cre-dependent, tamoxifen-inducible labeling of SMCs equivalent to the widely used
 Myh11-CreER
 
 T
 2
 
 mice. Labeling was equivalent in both male and female Cre
 +
 mice and was limited to vascular and visceral SMCs and pericytes in various tissues as assessed by immunofluorescence.
 
 
 
 
 
 We generated and validated the function of an autosomal
 Myh11-CreER
 
 T
 2
 
 -RAD
 mouse that can be used to assess sex as a biological variable with respect to the normal and pathophysiological functions of SMCs.
 
