B6.Cg-7630403G23Rik^{Tg(Th-cre)1Tmd}/J

Stock number: 008601
Product name: TH-Cre 1 , TH-1 Cre
Research areas: Neurobiology Research, Research Tools

Description

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.

In Goodwin et al. 2019 Genome Res. 29:494, it was discovered that the transgene integrated into chromosome 9 causing a 624 kbp deletion in the 7630403G23Rik locus.

Detailed description

These transgenic mice express Cre recombinase under the control of the rat tyrosine hydroxylase (TH) promoter. The transgene integrated into chromosome 9 causing a 624 kbp deletion in 7630403G23Rik locus. 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.

If the recombinase activity pattern of this allele is further characterized by the Genetic Resource Science group at The Jackson Laboratory, such findings will be reported on the Mouse Genome Informatics (MGI) Allele Detail entry (7630403G23Rik^{Tg(Th-cre)1Tmd}). This same information would also be found searching the MGI Recombinase Activity database.

Development

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 transgene integrated into chromosome 9 causing a 624 kbp deletion in 7630403G23Rik locus. Founder line 1 has a copy number of greater than 20. Founder line 1 has a copy number of 10-15 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.

Allele

Symbol: 7630403G23Rik^{Tg(Th-cre)1Tmd}
Name: transgene insertion 1, Ted M Dawson
MGI accession ID: MGI:3584380
Generation method: Transgenic
Attributes: Recombinase-expressing
Marker symbol: 7630403G23Rik
Marker name: RIKEN cDNA 7630403G23 gene
Chromosome: 9
Strain of origin: (C57BL/6 x SJL)F2
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: dopaminergic neurons
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. Line 1 inserted into the gene at 33514690-34139124 (Build GRCm38/mm10) resulting in a 624,434 bp deletion. Founder line 1 has a copy number of greater than 20.