STOCK Hdc^{tm1.1(icre)Wwis}/J

Stock number: 021198
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

The HDC-Cre mice express a codon optimized Cre recombinase (iCre) from the histidine decarboxylase (Hdc) promoter/enhancer elements. These mice may be useful for studying the role of histaminergic neurons.

Detailed description

Heterozygous HDC-Cre mice are viable and fertile, expressing an internal ribosome entry site (IRES)-iCre fusion protein from the histidine decarboxylase (Hdc) promoter/enhancer elements. Hdc encodes the catalyzing enzyme involved in the formation of histamine which is released during allergic reactions and acts as a neurotransmitter in the brain. Histaminergic neurons regulate sleep-wake cycle. When Hdc is induced, cre recombinase is expressed in tuberomammillary nucleus (TMN) of the hypothalamus as well as other areas of the brain, mast cells, gastric mucosa, and fetal liver. When these mice are bred with mice containing loxP-flanked sequence, Cre-mediated recombination will result in deletion of the floxed sequences in the Hdc-expressing cells of the offspring. The donating investigator has not attempted to generate homozygous mice to date (March 2013).

For example when bred to STOCK Gabrg2^tm1Wul/J mice (Stock No. 021197), GABAA receptors in these GABAA receptor γ2 subunit deficient histaminergic neurons exhibit increased excitability with no effect on the sleep-wake cycle.

Development

A targeting vector was designed to insert an internal ribosome entry site (IRES)-codon optimized Cre recombinase (iCre) fusion protein and frt-flanked neomycin resistance (neo) cassette between the stop codon and the polyadenylation signal into exon 12 of the histidine decarboxylase (Hdc) gene. Specifically, this cassette was placed between the stop codon and polyadenylation sequence of Hdc. This construct was electroporated into hybrid (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric mice were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette. Subsequently, these HDC-Cre mice were bred to C57BL/6J mice to remove the Flp-expressing transgene. These mice were maintained on a mixed background and also contained the Gabrg2^tm1Wul allele, which was removed prior to shipping. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Allele

Symbol: Hdc^{tm1.1(icre)Wwis}
Name: targeted mutation 1.1, William Wisden
MGI accession ID: MGI:5461698
Generation method: Targeted
Attributes: Recombinase-expressing
Marker symbol: Hdc
Marker name: histidine decarboxylase
Chromosome: 2
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Site of expression: When Hdc is induced, cre recombinase is expressed in tuberomammillary nucleus of the hypothalamus as well as other areas of the brain, mast cells, gastric mucosa, and fetal liver.
Molecular note: A targeting vector was generated to insert an improved IRES2i site, a humanized cre open reading frame and an FRT-flanked neo selection cassette into exon 12 of histidine decarboxylase between the stop codon and polyadenylation sequence, by homologous recombination in ES cells. Chimeras were produced by ES cell injection into C57BL/6J blastocysts. The resulting line was bred with Flp deleter mice to remove the neo cassette.