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Synaptotagmin 2 is ectopically overexpressed in a widely used CaMK2a-Cre mouse line [T29-1 dataset]

ABSTRACT: 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 show the results of differential expression analyses in the hippocampi of Cre+/- mice and wild-type littermates from the most widely used CaMKIIa-Cre line, Tg(Camk2a-cre)T29-1Stl (or T29-1). Results show differential expression of many genes including significant upregulation of St6gal2, a gene encoding beta-galactoside alpha-2,6-sialyltransferase 2, in the Cre+/- hippocampi. The physiological role of St6gal2 is not well studied, but it is implicated in schizophrenia and autism. These unexpected results may affect the interpretation of the results from studies using the T29-1 line and raise awareness of potential pitfalls in the use of Cre driver lines in general.

ORGANISM(S): Mus musculus

PROVIDER: GSE179802 | GEO | 2022/06/24

REPOSITORIES: GEO

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

Project description: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.

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