Similar Datasets
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.
2022-06-24 | GSE179803 | GEO
Project description:The CaMKΙΙα-Cre mouse lines, possibly the most used Cre lines in neuroscience, have resulted in over 800 articles to date. Here, we demonstrate that the second most widely used CaMKΙΙα-Cre line, Tg(Camk2a-cre)2Gsc (or CamiCre), shows ectopic overexpression of synaptotagmin 2, the most efficient Ca2+ sensor for fast synchronous neurotransmitter release, in excitatory presynapses of Cre+ brains. Moreover, the upregulation of immediate-early genes and genes incorporated in bacterial artificial chromosome (BAC) transgenes, such as L-proline transporter Slc6a7, was found in Cre+ hippocampus. The copy number and integration site of the transgene are suggested to have caused the aberrant gene expression in Cre+ brains. Most importantly, CamiCre+ mice showed functional phenotypes, such as hyperactivity and enhanced associative learning, suggesting that neural activities are affected. These unexpected results suggest difficulties in interpreting results from studies using the CamiCre line and raise a warning of potential pitfalls in using Cre driver lines in general.
| S-EPMC9287804 | biostudies-literature
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 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.
2022-06-24 | GSE179802 | GEO
Project description:Synaptotagmin 2 is ectopically overexpressed in a widely used CaMK2a-Cre mouse line
| PRJNA745106 | ENA
Project description:Synaptotagmin 2 is ectopically overexpressed in a widely used CaMK2a-Cre mouse line [CamiCre dataset]
| PRJNA745146 | ENA
Project description:Synaptotagmin 2 is ectopically overexpressed in a widely used CaMK2a-Cre mouse line [T29-1 dataset]
| PRJNA745104 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-06-24 | GSE129577 | GEO
Project description:Conditional gene targeting in mice has provided great insight into the role of gene function in kidney development and disease. Although a number of Cre-driver mouse strains already exist for the kidney, development of additional strains with unique expression patterns is needed. Here we report the generation and validation of a Tcf21/Pod1-Cre driver strain that expresses Cre recombinase throughout the condensing and stromal mesenchyme of developing kidneys and in their derivatives including epithelial components of the nephron and interstitial cells. To test the efficiency of this line, we crossed it to mice transgenic for either loss or gain of function ?-catenin conditional alleles. Mice with deletion of ?-catenin from Tcf21-expressing cells are born with hypoplastic kidneys, hydroureters and hydronephrosis. By contrast, Tcf21-Cre driven gain of function for ?-catenin in mice results in fused midline kidneys and hypoplastic kidneys. Finally, we report the first renal mesenchymal deletion of Patched1 (Ptch1), the receptor for sonic hedgehog (Shh), which results in renal cysts demonstrating a functional role of Shh signaling pathway in renal cystogensis. In summary, we report the generation and validation of a new Cre driver strain that provides robust excision in metanephric mesenchyme.
| S-EPMC3391250 | biostudies-literature
Project description:The Wnt1-Cre transgenic mouse line is extensively used in the study of the development of the neural crest and its derivatives and the midbrain. The Wnt1 gene has important developmental roles in formation of the midbrain-hindbrain boundary, regulation of midbrain size, and neurogenesis of ventral midbrain dopaminergic (mDA) neurons. Here, we report that Wnt1-Cre transgenic mice exhibit phenotypes in multiple aspects of midbrain development. Significant expansion of the midbrain and increased proliferation in the developing inferior colliculus is associated with ectopic expression of Wnt1. Marked elevation of Wnt1 expression in the ventral midbrain is correlated with disruption of the differentiation program of ventral mDA neurons. We find that these phenotypes can be attributed to ectopic expression of Wnt1 from the Wnt1-Cre transgene leading to the ectopic activation of canonical Wnt/?-catenin signaling. Since these caveats could complicate the utility of Wnt1-Cre in some developmental circumstances, we report a new Wnt1-Cre2 transgenic mouse line that can serve the same purposes as the original without the associated phenotypic complications. These studies reveal an important caveat to a widely-used reagent, provide an improved version of this reagent, and indicate that the original Wnt1-Cre transgenic mouse line may be useful as a gain of function model for interrogating Wnt signaling mechanisms in multiple aspects of midbrain development.
| S-EPMC3804302 | biostudies-literature
Project description:Camk2a-Cre mice have been widely used to study the postnatal function of several genes in forebrain projection neurons, including cortical projection neurons (CPNs) and striatal medium-sized spiny neurons (MSNs). We linked heterozygous deletion of TSHZ3/Tshz3 gene to autism spectrum disorder (ASD) and used Camk2a-Cre mice to investigate the postnatal function of Tshz3, which is expressed by CPNs but not MSNs. Recently, single-cell transcriptomics of the adult mouse striatum revealed the expression of Camk2a in interneurons and showed Tshz3 expression in striatal cholinergic interneurons (SCINs), which are attracting increasing interest in the field of ASD. These data and the phenotypic similarity between the mice with Tshz3 haploinsufficiency and Camk2a-Cre-dependent conditional deletion of Tshz3 (Camk2a-cKO) prompted us to better characterize the expression of Tshz3 and the activity of Camk2a-Cre transgene in the striatum. Here, we show that the great majority of Tshz3-expressing cells are SCINs and that all SCINs express Tshz3. Using lineage tracing, we demonstrate that the Camk2a-Cre transgene is expressed in the SCIN lineage where it can efficiently elicit the deletion of the Tshz3-floxed allele. Moreover, transcriptomic and bioinformatic analysis in Camk2a-cKO mice showed dysregulated striatal expression of a number of genes, including genes whose human orthologues are associated with ASD and synaptic signaling. These findings identifying the expression of the Camk2a-Cre transgene in SCINs lineage lead to a reappraisal of the interpretation of experiments using Camk2a-Cre-dependent gene manipulations. They are also useful to decipher the cellular and molecular substrates of the ASD-related behavioral abnormalities observed in Tshz3 mouse models.
| S-EPMC8328143 | biostudies-literature