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(Circulation Research. 2007;101:e124.)
© 2007 American Heart Association, Inc.

Letter to the Editor

Targeted Rearrangement of Floxed Alleles in Smooth Muscle Cells in Vivo

Andrew D. Frutkin, Haikun Shi, Goro Otsuka, David A. Dichek

Department of Medicine, University of Washington, Seattle

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

In their biologically and technically important article "Development of a Smooth Muscle-targeted Cre Recombinase Mouse Reveals Novel Insights Regarding Smooth Muscle Myosin Heavy Chain Promoter Regulation",¹ Regan et al reported generation of mice that express cre recombinase from a fragment of the smooth muscle myosin heavy chain (SMMHC) promoter. The biological importance of this article was that it provided strong evidence of either temporally or spatially restricted expression of the SMMHC promoter in smooth muscle cells in vivo. The paper also had two important technical aspects. First, it demonstrated that expression of a SMMHC promoter-cre construct in cre-indicator mice was a more sensitive means of detecting promoter activity than a construct in which the SMMHC promoter expressed lacZ. Second, the SMMHC-cre mice themselves were said to "provide a powerful tool to researchers to study gene function in vascular development/disease by using cre/lox technology to direct smooth-muscle-specific gene activation or inactivation."

Although the SMMHC-cre mice reported by Regan et al have been used by one group for gene activation,^2,3 we—as well as other groups that shared their results with us⁴—found that these mice do not efficiently inactivate floxed alleles in smooth muscle lineages.⁴ In addition, we found that the cre expression in these SMMHC-cre mice was not restricted to SMC lineages. Specifically, our efforts to use the SMMHC-cre mice to inactivate a floxed allele for the type 2 transforming growth factor beta receptor (tgfbr2^flox)⁵ yielded the following results: (1) SMMHC-cre mice inefficiently rearranged both tgfbr2^flox . . . [Full Text of this Article]