September 12, 2007 | Shiaoching Gong, Martin Doughty, Carroll R. Harbaugh, Alexander Cummins, Mary E. Hatten, Nathaniel Heintz, and Charles R. Gerfen
This study describes the generation of 14 BAC-Cre transgenic mouse lines, each expressing Cre recombinase in specific neuronal and glial populations in the brain. These lines were created using bacterial artificial chromosome (BAC) constructs containing the promoters of 10 genes, including Chat, Th, Slc6a4, Slc6a2, Etv1, Ntsr1, Drd2, Drd1, Pcp2, and Cmtm5. These BAC-Cre lines add functional utility to the >500 BAC-EGFP transgenic mouse lines available in the Gene Expression Nervous System Atlas (GENSAT) project.
The ability to target genetic manipulations to specific CNS cell types is essential for analyzing genes, cells, and circuits involved in behavior and disease. The study demonstrates that BAC-Cre constructs can be used to efficiently drive functional levels of Cre recombinase in specific cell types. The BAC vectors used in this study are capable of accommodating dispersed regulatory sequences across large regions of the genome, allowing for reproducible expression of the target gene.
The study reports that all 10 BAC-Cre vectors tested produced functional Cre expression in the expected cell types, including one inducible with tamoxifen. The patterns of Cre-induced EGFP expression varied, which is instructive for the general use of BACs to direct Cre expression in targeted neuronal and glial cell types. The study also highlights the utility of BAC-Cre constructs for targeting specific neurotransmitter systems, such as the serotonin transporter (Slc6a4), and for targeting specific forebrain circuits, such as those involving the dopamine receptors Drd1a and Drd2.
The study also describes the generation of BAC-Cre transgenic lines for two other genes, Pcp2 and Cmtm5, which are expressed in specific neuron types, such as Purkinje cells and oligodendrocytes. These lines produce specific Cre expression in the appropriate brain cell types. Additionally, the study describes the generation of an inducible Cre expression line using the Slc6a4 BAC-ER-Cre construct, which allows for the controlled expression of Cre in serotonin neurons.
The study concludes that BAC-Cre constructs are a valuable resource for generating transgenic mouse lines in which Cre recombinase expression is directed to specific neuron and glial cell types. These lines can be used to study gene function in specific cell populations and to investigate the complex mechanisms of disease. The 14 BAC-Cre lines described in this study will be added to the GENSAT BAC-EGFP lines and distributed through the Mutant Mouse Regional Resource Center (MMRRC). The patterns of Cre expression for these lines will be provided on the GENSAT website, which will include data from adult brain sections and from developmental patterns as appropriate.This study describes the generation of 14 BAC-Cre transgenic mouse lines, each expressing Cre recombinase in specific neuronal and glial populations in the brain. These lines were created using bacterial artificial chromosome (BAC) constructs containing the promoters of 10 genes, including Chat, Th, Slc6a4, Slc6a2, Etv1, Ntsr1, Drd2, Drd1, Pcp2, and Cmtm5. These BAC-Cre lines add functional utility to the >500 BAC-EGFP transgenic mouse lines available in the Gene Expression Nervous System Atlas (GENSAT) project.
The ability to target genetic manipulations to specific CNS cell types is essential for analyzing genes, cells, and circuits involved in behavior and disease. The study demonstrates that BAC-Cre constructs can be used to efficiently drive functional levels of Cre recombinase in specific cell types. The BAC vectors used in this study are capable of accommodating dispersed regulatory sequences across large regions of the genome, allowing for reproducible expression of the target gene.
The study reports that all 10 BAC-Cre vectors tested produced functional Cre expression in the expected cell types, including one inducible with tamoxifen. The patterns of Cre-induced EGFP expression varied, which is instructive for the general use of BACs to direct Cre expression in targeted neuronal and glial cell types. The study also highlights the utility of BAC-Cre constructs for targeting specific neurotransmitter systems, such as the serotonin transporter (Slc6a4), and for targeting specific forebrain circuits, such as those involving the dopamine receptors Drd1a and Drd2.
The study also describes the generation of BAC-Cre transgenic lines for two other genes, Pcp2 and Cmtm5, which are expressed in specific neuron types, such as Purkinje cells and oligodendrocytes. These lines produce specific Cre expression in the appropriate brain cell types. Additionally, the study describes the generation of an inducible Cre expression line using the Slc6a4 BAC-ER-Cre construct, which allows for the controlled expression of Cre in serotonin neurons.
The study concludes that BAC-Cre constructs are a valuable resource for generating transgenic mouse lines in which Cre recombinase expression is directed to specific neuron and glial cell types. These lines can be used to study gene function in specific cell populations and to investigate the complex mechanisms of disease. The 14 BAC-Cre lines described in this study will be added to the GENSAT BAC-EGFP lines and distributed through the Mutant Mouse Regional Resource Center (MMRRC). The patterns of Cre expression for these lines will be provided on the GENSAT website, which will include data from adult brain sections and from developmental patterns as appropriate.