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An X‐linked Myh11‐CreER T2 mouse line resulting from Y to X chromosome‐translocation of the Cre allele
Author(s) -
Liao Mingmei,
Zhou Junmei,
Wang Fen,
Ali Yasmin H.,
Chan Kelvin L.,
Zou Fei,
Offermanns Stefan,
Jiang Zhisheng,
Jiang Zhihua
Publication year - 2017
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.23054
Subject(s) - biology , allele , microbiology and biotechnology , chromosomal translocation , x chromosome , genetically modified mouse , transgene , genetics , gene
Summary The Myh11‐CreER T2 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/Y Cre+ ), 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/X Cre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/Y Cre+ mice. This mosaicism, however, diminished in homozygous X Cre+ /X Cre+ mice. In a model of aortic aneurysm induced by a SMC‐specific Tgfbr1 deletion, the homozygous X Cre+ /X Cre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/X Cre+ 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 X Cre+ /X Cre+ mice produce uniform Cre activity in arterial SMCs.