An X‐linked Myh11‐CreERT2 mouse line resulting from Y to X chromosome‐translocation of the Cre allele |
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Authors: | Fen Wang Yasmin H Ali Kelvin L Chan Fei Zou Stefan Offermanns Zhisheng Jiang Zhihua Jiang |
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Institution: | 1. Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, Florida;2. Department of Biostatistics, University of Florida College of Public Health & Health Professions College of Medicine, Gainesville, Florida;3. Max‐Planck‐Institute for Heart and Lung Research, University of Heidelberg, Bad Nauheim, Germany;4. Institute of Cardiovascular Disease, University of South China, Hengyang, China |
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Abstract: | The Myh11‐CreERT2 mouse line (Cre+) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/YCre+), which excluded its application in female mice. Our group established a Cre+ colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X‐linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/XCre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/YCre+ mice. This mosaicism, however, diminished in homozygous XCre+/XCre+ mice. In a model of aortic aneurysm induced by a SMC‐specific Tgfbr1 deletion, the homozygous XCre+/XCre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/XCre+ Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X‐inactivation. The homozygous XCre+/XCre+ mice produce uniform Cre activity in arterial SMCs. |
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Keywords: | genetics mammal mutagenesis organism process tissue vasculature |
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