STOCK Tg(dlx5a-cre)1Mekk/J

Stock number: 008199
Product name: Dlx5/6-Cre
Research areas: Neurobiology Research, Research Tools

Description

These Dlx5/6-Cre transgenic mice have Cre recombinase expression directed by the regulatory sequences of the zebrafish dlx5a/dlx6a genes and may be useful in generating specific deletions of floxed alleles in GABAergic in forebrain and other brain regions.

Detailed description

Homozygous Dlx5/6-Cre transgenic mice are viable and fertile. Expression of Cre recombinase (Cre) is directed to differentiating and migrating forebrain GABAergic neurons during embryonic development by the I56i and I56ii enhancers from the zebrafish dlx5a/dlx6a intergenic region (with the 5' promoter region of zebrafish dlx6a in place to increase the activity of the intergenic enhancers rather than direct tissue-specific expression). When Dlx5/6-Cre transgenic mice are bred with mice containing a loxP-flanked sequence, Cre-mediated recombination will result in deletion of the floxed sequence in the offspring. These Dlx5/6-Cre transgenic mice may be useful in generating specific deletions of floxed alleles in GABAergic neurons in forebrain and other brain regions.

Luo et al. 2020 Neuron 106:37 Table 1 shows germline recombination in offspring (F2) of Cre;floxed double mutant (F1) mice bred to floxed and/or wildtype mice. The authors also note that in general, the frequency of recombination in Cre;floxed double mutant germline cells appears to be considerably higher than in zygotes produced by breeding Cre mice to floxed mice.
This reports that Dlx5/6-Cre;floxed double mutant females bred to floxed and/or wildtype males produced some offspring with germline deletion of the floxed allele [observed from several cohorts (including up to 85.3% (29/34) of Cre negative offspring)]. As such, for Cre-lox experiments and to avoid/minimize germline deletion of the floxed allele, researchers may consider breeding Dlx5/6-Cre males to floxed females.

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. For endogenous mouse gene expression, information may also be found searching the MGI Recombinase Activity and MGI Gene Expression + Recombinase Activity Comparison Matrix.

Development

The Dlx5/6-Cre transgene was designed with a 3.5 kb fragment from the immediate 5'-flanking region of zebrafish dlx6a gene (including part of the 5' UTR) placed immediately upstream of a Cre recombinase coding sequence, all followed by a 1.4 kb enhancer fragment from the zebrafish dlx5a/dlx6a intergenic region (containing both zebrafish I56i and I56ii enhancers). The donating investigator reports that a female founder mouse (founder #8561 on a CD1 genetic background) was bred to CD1 males and the resulting Dlx5/6-Cre mice were maintained by breeding hemizygous males with CD1 females for at least 10 generations prior to arrival at The Jackson Laboratory Repository. Upon arrival, transgenic animals were bred with C57BL/6J mice for at least one generation to establish the colony.

Allele

Symbol: Tg(dlx5a-cre)1Mekk
Name: transgene insertion 1, Marc Ekker
MGI accession ID: MGI:3758328
Generation method: Transgenic
Attributes: Recombinase-expressing
Marker symbol: Tg(dlx5a-cre)1Mekk
Marker name: transgene insertion 1, Marc Ekker
Chromosome: UN
Strain of origin: CD-1
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: GABAergic forebrain neurons
Molecular note: A cre gene was placed under the control of the I56i and I56ii enhancer elements of zebrafish dlx5a and a 3.5kb genomic DNA fragment flanking the 5' region of the zebrafish dlx6a open reading frame and containing the 5'UTR. The dlx6a flanking region on its own cannot produce tissue specific expression but increases the activity of the enhancers to produce expression that recapitulate endogenous Dlx5 expression. Tissue specific expression was confirmed by test crosses to reporter mice strains, including Tg(ACTB-Bgeo/ALPP)1Lbe, Tg(ACTB-Bgeo/GFP)21Lbe and Gt(ROSA)26Sor^tm1Sor.