These transgenic mice ("SLICK" for single-neuron labeling with inducible Cre-mediated knock-out) have a tamoxifen inducible Cre-mediated recombination system and Enhanced Yellow Fluorescent Protein driven by 2 bidirectional copies of the mouse thymus cell antigen 1 promoter. Hemizygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The Donating Investigator has not attempted to make the strain homozygous. When crossed with a strain containing a loxP site flanked sequence of interest, the offspring are useful for generating tamoxifen-induced, Cre-mediated targeted neuron-specific deletions only in neurons where the Thy1 promoter is active. These cells will be evident by the expression of Yellow Fluorescent Protein. Transgenic mice express YFP constitutively in neurons. The Donating Investigator reports that founder line A (SLICK-A) mice express the transgene in small subsets of motor neurons and dorsal root ganglion neurons.

Further characterization [Heimer-McGinn and Young 2011 genesis 49:942] reports that SLICK-A mice have high YFP fluorescence in some hippocampal regions and cortical layer V, but sparse/dim labeling in other regions (such as the midbrain and brainstem). Fluorescence is less uniform, but this allows single-neuron labeling. SLICK-A mice exhibit significant cre-mediated recombination in the absence of tamoxifen. This "leaky" recombination in SLICK-A mice was prominent in areas that have bright YFP labeling (such as hippocampal CA1 and cortical layer V). Following tamoxifen-induction, efficient recombination is observed in the expected cell types, but with some inefficient recombination observed as well (including hippocampal CA3 and cortical layers II/III). This publication concluded that YFP and cre^ERT2 expression levels are tightly coupled in SLICK-A mice, and that excessive levels of cre^ERT2 must be avoided to achieve tight control of recombinase activity when using SLICK-A mice.

The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.

This strain is one of many from the same transgene creator/donating investigator with fluorescent protein expression/neurobiological research applications, including:
SLICK line A (Stock No. 007606), SLICK line V (Stock No. 007610), SLICK line H (Stock No. 012708), GAD67-GFP line 3 (Stock No. 007673),Thy1-GFP line O (Stock No. 007919), Thy1-YFP line G (line 17) (Stock No. 014130),Thy1-CFP line I (Stock No. 014131), Thy1-ChR2-YFP line 18 (Stock No. 007612), Thy1-ChR2-YFP line 9 (Stock No. 007615), Thy1-eNpHR-YFP line 2 (Stock No. 012332), Thy1-eNpHR-YFP line 4 (Stock No. 012334), Thy1-vChR1-YFP line 1 (Stock No. 012341), Thy1-vChR1-YFP line 4 (Stock No. 012344), Thy1-vChR1-YFP line 8 (Stock No. 012348), Thy1-mhChR2-YFP line 20 (Stock No. 012350), Prv-mhChR2-YFP line 15 (Stock No. 012355), ChAT-ChR2-YFP line 5 (Stock No. 014545), ChAT-ChR2-YFP line 6 (Stock No. 014546), VGAT-ChR2-YFP line 8 (Stock No. 014548), TpH2-ChR2-YFP line 5 (Stock No. 014555), and R26-CAG-LSL-2XChETA-tdTomato reporter mice (Stock No. 017455).

Development

A transgenic construct containing the cre/ESR1 fusion gene (CreER^T2), enhanced Yellow Fluorescent Protein under the control of 2 copies (placed back to back to function bidirectionally) of the mouse thymus cell antigen 1 promoter was microinjected into C57BL/6 X SJL F1 donor eggs. Founder line A was subsequently established. The mice were backcrossed to C57BL/6 for 6 generations.

Expression Data

Expressed Gene	YFP, Yellow Fluorescent Protein, jellyfish
Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	tamoxifen-inducible Cre and YFP in subsets of motor neurons and dorsal root ganglion neurons, and in many neurons of the cortex, hippocampus (both CA1 and dentate granule cells) and cerebellar mossy fibers

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Deisseroth K; Feng G; Majewska AK; Miesenbock G; Ting A; Schnitzer MJ. 2006. Next-generation optical technologies for illuminating genetically targeted brain circuits. J Neurosci 26(41):10380-6. PubMed: 17035522 MGI: J:122791
Young P; Qiu L; Wang D; Zhao S; Gross J; Feng G. 2008. Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice. Nat Neurosci :. PubMed: 18454144 MGI: J:134019

View All References

Genetics

Tg(Thy1-cre/ERT2,-EYFP)AGfng

Allele Symbol: Tg(Thy1-cre/ERT2,-EYFP)AGfng

Allele Name	transgene insertion A, Guoping Feng
Allele Type	Transgenic (Inducible, Recombinase-expressing, Reporter)
Allele Synonym(s)	SLICK line A; SlickA; Tg(Thy1-cre/ESR1,-EYFP)Agfng
Gene Symbol and Name	Tg(Thy1-cre/ERT2,-EYFP)AGfng, transgene insertion A, Guoping Feng
Gene Synonym(s)	SLICK line A; Tg(Thy1-cre/ESR1,-EYFP)AGfng; Tg(Thy1-cre/ESR1,-EYFP)AGfng
Promoter	Thy1, thymus cell antigen 1, theta, mouse, laboratory
Expressed Gene	YFP, Yellow Fluorescent Protein, jellyfish
Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	tamoxifen-inducible Cre and YFP in subsets of motor neurons and dorsal root ganglion neurons, and in many neurons of the cortex, hippocampus (both CA1 and dentate granule cells) and cerebellar mossy fibers
Strain of Origin	(C57BL/6 x SJL)F1
Chromosome	UN
Molecular Note	Transgenic mice have a tamoxifen inducible Cre-mediated recombination system and Enhanced Yellow Fluorescent Protein driven by 2 bidirectional copies of the mouse thymus cell antigen 1 promoter.
Mutations Made By	Guoping Feng, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Cre-lox System
  - Cre Recombinase expression in neural tissue
- Fluorescent protein expression in neural tissue
Research Tools
- Cre-lox System
  - Cre Recombinase Expression
  - Cre Recombinase Expression: Inducible
- Fluorescent Proteins
- Neurobiology Research
  - cell marker

Genotype: YFP related

Research Tools
- Fluorescent Proteins

References

Deisseroth K; Feng G; Majewska AK; Miesenbock G; Ting A; Schnitzer MJ. 2006. Next-generation optical technologies for illuminating genetically targeted brain circuits. J Neurosci 26(41):10380-6. PubMed: 17035522 MGI: J:122791
Young P; Qiu L; Wang D; Zhao S; Gross J; Feng G. 2008. Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice. Nat Neurosci :. PubMed: 18454144 MGI: J:134019

Additional - Tg(Thy1-cre/ERT2,-EYFP)AGfng related

Fricker FR; Lago N; Balarajah S; Tsantoulas C; Tanna S; Zhu N; Fageiry SK; Jenkins M; Garratt AN; Birchmeier C; Bennett DL. 2011. Axonally derived Neuregulin-1 is required for remyelination and regeneration after nerve injury in adulthood. J Neurosci 31(9):3225-33. PubMed: 21368034 MGI: J:170675
Heimer-McGinn V; Young P. 2011. Efficient inducible Pan-neuronal cre-mediated recombination in SLICK-H transgenic mice. Genesis 49(12):942-9. PubMed: 21671347 MGI: J:180876
Samuel MA; Valdez G; Tapia JC; Lichtman JW; Sanes JR. 2012. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions. PLoS One 7(10):e46663. PubMed: 23056392 MGI: J:192104
Thakar S; Wang L; Yu T; Ye M; Onishi K; Scott J; Qi J; Fernandes C; Han X; Yates JR 3rd; Berg DK; Zou Y. 2017. Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation. Proc Natl Acad Sci U S A 114(4):E610-E618. PubMed: 28057866 MGI: J:239529
Wilhelm JC; Xu M; Cucoranu D; Chmielewski S; Holmes T; Lau KS; Bassell GJ; English AW. 2012. Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration. J Neurosci 32(14):5002-9. PubMed: 22492055 MGI: J:184131

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