Germ line activation of the Tie2 and SMMHC promoters causes noncell-specific deletion of floxed alleles.
Tissue-specific knockouts generated through Cre-loxP recombination have become an important tool to manipulate the mouse genome. Normally, two successive rounds of breeding are performed to generate mice carrying two floxed target-gene alleles and a transgene expressing Cre-recombinase tissue-specifically. We show herein that two promoters commonly used to generate endothelium-specific (Tie2) and smooth muscle-specific [smooth muscle myosin heavy chain (Smmhc)] knockout mice exhibit activity in the female and male germ lines, respectively. This can result in the inheritance of a null allele in the second generation that is not tissue specific. Careful experimental design is required therefore to ensure that tissue-specific knockouts are indeed tissue specific and that appropriate controls are used to compare strains.
de Lange
Willem J
WJ
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Halabi
Carmen M
CM
Beyer
Andreas M
AM
Sigmund
Curt D
CD
D000483:Alleles; D000818:Animals; D005260:Female; D005854:Germ Cells / Q000378:metabolism*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D042787:Receptor, TIE-2 / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D019076:Transgenes
D042787:Receptor, TIE-2; C045073:Cre recombinase; D019426:Integrases; D018995:Myosin Heavy Chains