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Background  Despite a number of different transgenes that can mediate DNA deletion in the developing lens, each has unique features that can make a given transgenic line more or less appropriate for particular studies. The purpose of this work encompasses both a review of transgenes that lead to the expression of Cre recombinase in the lens and a comparative analysis of currently available transgenic lines with a particular emphasis on the  Le-Cre  and  P0-3.9GFPCre  lines that can mediate DNA deletion in the lens placode. Although both of these transgenes are driven by elements of the  Pax6  P0 promoter, the  Le-Cre  transgene consistently leads to ocular abnormalities in homozygous state and can lead to ocular defects on some genetic backgrounds when hemizygous.    Result  Although both  P0-3.9GFPCre  and  Le-Cre  hemizygous transgenic mice undergo normal eye development on an  FVB/N  genetic background,  Le-Cre  homozygotes uniquely exhibit microphthalmia. Examination of the expression patterns of these two transgenes revealed similar expression in the developing eye and pancreas. However, lineage tracing revealed widespread non-ocular CRE reporter gene expression in the  P0-3.9GFPCre  transgenic mice that results from stochastic CRE expression in the  P0-3.9GFPCre  embryos prior to lens placode formation. Postnatal hemizygous  Le-Cre  transgenic lenses express higher levels of CRE transcript and protein than the hemizygous lenses of  P0-3.9GFPCre  mice. Transcriptome analysis revealed that  Le-Cre  hemizygous lenses deregulated the expression of 15 murine genes, several of which are associated with apoptosis. In contrast,  P0-3.9GFPCre  hemizygous lenses only deregulated two murine genes. No known PAX6-responsive genes or genes directly associated with lens differentiation were deregulated in the hemizygous  Le-Cre  lenses.    Conclusions  Although  P0-3.9GFPCre  transgenic mice appear free from ocular abnormalities, extensive non-ocular CRE expression represents a potential problem for conditional gene deletion studies using this transgene. The higher level of CRE expression in  Le-Cre  lenses versus  P0-3.9GFPCre  lenses may explain abnormal lens development in homozygous  Le-Cre  mice. Given the lack of deregulation of PAX6-responsive transcripts, we suggest that abnormal eye development in  Le-Cre  transgenic mice stems from CRE toxicity. Our studies reinforce the requirement for appropriate CRE-only expressing controls when using CRE as a driver of conditional gene targeting strategies.    Electronic supplementary material  The online version of this article (10.1186/s40246-019-0192-8) contains supplementary material, which is available to authorized users.

Considerations for the use of Cre recombinase for conditional gene deletion in the mouse lens