TH-Cre transgenic mice have the rat tyrosine hydroxylase (TH) promoter directing expression of Cre recombinase to catecholaminergic cells, and may be useful for generating conditional mutations in these cells for studying dopaminergic cell function, Parkinson's disease, and other neurodegenerative disorders.
Ted M Dawson, Johns Hopkins Univ School of Medicine
Mice hemizygous for the TH-Cre transgene are viable and fertile, with the rat tyrosine hydroxylase (TH) promoter directing expression of Cre recombinase to catecholaminergic cells. Using crosses to reporter strains, cre activity is confirmed in catecholaminergic cells and is present in many of the projection areas of these neuronal populations. A mosaic of cre activity is noted in TH-positive neurons. Several other areas that are not typically thought to have active TH expression, including the lateral septal nucleus, accessory olfactory bulb, suparafascicular thalamus, and pretectal area, also exhibit Cre recombinase activity (possibly as a result of TH promoter activity in precursor cell populations or ectopic expression from the exogenous TH promoter). Some TH-negative cells closely clustered around and within TH-positive nuclei demonstrate cre activity. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequence(s) in the offspring. These TH-Cre transgenic mice are a tool for generating conditional mutations in catecholaminergic cells and may be useful for studying dopaminergic cell function, Parkinson's disease, and other neurodegenerative disorders.
The TH-Cre transgene was designed with a 9.0 kb fragment of the rat tyrosine hydroxylase (TH) promoter, synthetic 5' UTR intron, cre cDNA, and SV40 late region polyadenylation site. The transgene was microinjected into the pronuclei of fertilized B6/SJLF2 oocytes. Founder mice were bred to C57BL/6NCrl to confirm germline transmission and establish founder line 1 (TH-Cre 1). The donating investigator reported that the TH-Cre 1 transgenic colony was subsequently maintained by backcrossing to C57BL/6 (Charles River) mice for greater than five generations prior to arrival at The Jackson Laboratory Repository in 2009. Upon arrival, transgenic mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) to establish the colony. Thereafter, the colony was maintained by breeding hemizygous mice with wildtype (noncarrier) mice from the colony. In 2014, SNP analysis suggests these mice are predominantly on a C57BL/6N genetic background (see SNP note below).
In 2010 and 2011, a 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony (generation N6+F2, N6+F4 and N6+F6) at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating (each mouse having at least 1 marker segregating). These data suggest the mice sent to The Jackson Laboratory Repository in 2009 were on a C57BL/6J or mixed C57BL/6J;C57BL/6N genetic background. In 2014, a cohort of mice from generation N6+F14 had 4 of the 5 markers that determine C57BL/6J from C57BL/6N fixed to C57BL/6N allele-type, with a single marker on chromosome 13 (~41.0 Mbp) fixed to C57BL/6J allele-type.
|Expressed Gene||cre, cre recombinase, bacteriophage P1|
|Site of Expression||dopaminergic neurons|
|Allele Name||transgene insertion 1, Ted M Dawson|
|Allele Type||Transgenic (Recombinase-expressing)|
|Gene Symbol and Name||Tg(Th-cre)1Tmd, transgene insertion 1, Ted M Dawson|
|Promoter||Th, tyrosine hydroxylase, rat|
|Expressed Gene||cre, cre recombinase, bacteriophage P1|
|Site of Expression||dopaminergic neurons|
|Strain of Origin||(C57BL/6 x SJL)F2|
|Molecular Note||Cre recombinase is expressed under the control of the rat tyrosine hydroxylase promoter. Cre recombinase activity is detected in catecholaminergic cells. This is a representative record representing TH-cre1 - TH-cre5 all of which have identical activity. The authors state that TH-cre4 appears to be X-linked.|
|Mutations Made By|| |
Ted Dawson, Johns Hopkins Univ School of Medicine
When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304). The donating investigator reports that homozygous mice are viable.
When using the B6.Cg-Tg(Th-cre)1Tmd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008601 in your Materials and Methods section.
|Hemizygous or Non carrier for Tg(Th-cre)1Tmd|
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