Synaptotagmin 2 is ectopically overexpressed in a widely used CaMK2a-Cre mouse line [CamiCre dataset]

The Cre-loxP system is one of the most powerful and commonly used techniques in neurogenetics, as well as in broad biomedical studies. The CaMKIIa-Cre mouse line, one of the earliest established Cre driver lines, has resulted in over 800 papers to date. While Cre driver lines are well characterized for Cre expression patterns, many are not well characterized for phenotypes. Here, we demonstrate that the second most widely used CaMKIIa-Cre line, Tg(Camk2a-cre)2Gsc (or CamiCre), shows significant overexpression of synaptotagmin 2, the most efficient Ca2+ sensor for fast synchronous neurotransmitter release, in Cre+/- hippocampus compared to wild-type littermates. Moreover, upregulation of immediate early genes, such as Arc and Fos, and genes presumably derived from bacterial artificial chromosome transgene, such as Slc6a7 were also observed in the Cre+/- hippocampus. These unexpected results suggest difficulties in interpreting results from studies using the CamiCre line and raise awareness of potential pitfalls in the use of Cre driver lines in general. HIppocampal RNA profiles of 9-week-old wild type (WT) and Tg(Camk2a-cre)2Gsc (CamiCre) Cre+/- mice