B6(Cg)-Hdac3^tm1.1Laz/J

Stock number: 024119
Product name: Hdac3^flox
Research areas: Cell Biology Research, Research Tools

Description

Hdac3^flox/flox mice may be useful for studying HDAC3-induced gene silencing.

Detailed description

These Hdac3^flox/flox mutant mice possess loxP sites flanking exons 4-7 of the histone deacetylase 3 (Hdac3) gene. HDAC3 is an enzyme that regulates the acetylation of histone tails by modulating histone-DNA interactions resulting in gene silencing. HDAC3-induced silencing is involved in cell growth, apoptosis, neuronal plasticity, tumor suppression, transcriptional regulation, cell cycle progression, and development. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 4-7 deleted in the cre-expressing tissues.

For example, 2 weeks after infusion of adenoviral Cre recombinase in area CA1 of the dorsal hippocampus, HDAC3 deficiency results in enhanced long term memory.

When bred to B6.Cg-Tg(Fabp4-cre)1Rev/J mice (Stock No. 005069) expressing Cre recombinase in brown and white gonadal and subcutaneous adipose tissue, 50% of offspring died by postnatal day 5; no mice survived to adulthood.

When bred to B6;FVB-Tg(Adipoq-cre)1Evdr/J mice (Stock No. 010803) expressing Cre recombinase in adipose tissue, offspring lived to at least 6 months.

Development

A targeting vector was designed to insert a loxP site upstream of exon 4, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 7 of the histone deacetylase 3 (Hdac3) gene. The construct was electroporated into C57BL/6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred to C57BL/6J females. Offspring were bred with ACT-Flpe transgenic mice on a C57BL/6 background to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Hdac3^tm1.1Laz
Name: targeted mutation 1.1, Mitchell A Lazar
MGI accession ID: MGI:4889069
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Hdac3
Marker name: histone deacetylase 3
Chromosome: 18
Strain of origin: C57BL/6
Molecular note: A loxP site was inserted upstream of exon 4. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 7. Flp-mediated recombination removed the neo cassette and left exons 4 through 7 floxed.