UMMS Affiliation

Department of Cell Biology; Department of Biochemistry and Molecular Pharmacology

Date

5-17-2011

Document Type

Article

Subjects

Transgenes; Integrases; MicroRNAs; Mice

Abstract

Transgenes flanked by loxP sites have been widely used to generate transgenic mice where the transgene expression can be controlled spatially and temporally by Cre recombinase. Data from this approach has led to important conclusions in cancer, neurodevelopment and neurodegeneration. Using this approach to conditionally express micro RNAs (miRNAs) in mice, we found that Cre-mediated recombination in neural progenitor cells caused microcephaly in five of our ten independent transgenic lines. This effect was not associated with the types or the quantity of miRNAs being expressed, nor was it associated with specific target knockdown. Rather, it was correlated with the presence of multiple tandem transgene copies and inverted (head-to-head or tail-to-tail) transgene repeats. The presence of these inverted repeats caused a high level of cell death in the ventricular zone of the embryonic brain, where Cre was expressed. Therefore, results from this Cre-loxP approach to generate inducible transgenic alleles must be interpreted with caution and conclusions drawn in previous reports may need reexamination.

Rights and Permissions

Citation: PLoS One. 2011 May 10;6(5):e18778. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

21572998

Journal Title

PloS one

Included in

Cell Biology Commons

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