Mid-facial developmental defects caused by the widely used LacZ reporter gene when expressed in neural crest-derived cells
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Reporter genes play important roles in transgenic research. LacZ is a widely used reporter gene that encodes Escherichia coli β-galactosidase, an enzyme that is well known for its ability to hydrolyze X-gal into a blue product. It is unknown whether transgenic LacZ has any adverse effects. R26R reporter mice, containing a LacZ reporter gene, were generated to monitor the in vivo recombination activity of various transgenic Cre recombinase via X-gal staining. P0-Cre is expressed in neural crest-derived cells, which give rise to the majority of the craniofacial bones. Herein, we report that 12% of the R26R reporter mice harboring P0-Cre had unexpected mid-facial developmental defects manifested by the asymmetrical growth of some facial bones, thus resulting in tilted mid-facial structure, shorter skull length, and malocclusion. Histological examination showed a disorganization of the frontomaxillary suture, which may at least partly explain the morphological defect in affected transgenic mice. Our data calls for the consideration of the potential in vivo adverse effects caused by transgenic β-galactosidase.
KeywordsR26R LacZ β-galactosidase Reporter gene P0-Cre Wnt1-Cre Transgenic mouse
We thank Neil Thomas for help in editing the manuscript. We also thank Drs. Marco Giovannini, Andrew McMahon, and Phillipe Soriano for genetically modified mouse lines. This work was supported by NIH (AR062030 to FL) and NSFC (81470764 to MH). Micro-CT work was partly supported by the P30 Core Center award to the University of Michigan from NIAMS (AR 69620).
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The authors declares that they have no conflict of interest.
- Chen CM, Krohn J, Bhattacharya S, Davies B (2011) A comparison of exogenous promoter activity at the ROSA26 locus using a PhiiC31 integrase mediated cassette exchange approach in mouse ES cells. PLoS ONE 6:e23376. https://doi.org/10.1371/journal.pone.0023376 CrossRefPubMedPubMedCentralGoogle Scholar