These mice carry a floxed allele of the Hdac2 (histone deacetylase 2) gene. Exons 5 and 6, encoding the HDAC-catalytic core of the protein, are flanked by loxP sites. Cre-mediated excision of the floxed segment results in a null genotype, lacking protein expression. HDAC2 deficiency results in increased synapse number and memory facilitation.
Li-Huei Tsai, Massachusetts Institue of Technology
Dr. Ronald DePinho, MD Anderson Cancer Center
Chromatin remodeling, especially through histone-tail acetylation, is emerging as a fundamental mechanism for regulating gene expression. Inhibition of histone deacetylases increases histone-tail acetylation and facilitates learning and memory in wildtype mice as well as in mouse models of neurodegeneration. HDAC2 (histone deacetylase 2) deficiency results in increased synapse number and memory facilitation.
These mice carry a floxed allele of the Hdac2 gene. Exons 5 and 6, encoding the HDAC-catalytic core of the protein, are flanked by loxP sites. Western blot analysis demonstrates that HDAC2 expression in floxed mice is similar to that of wildtype. Cre-mediated excision of the floxed segment results in a null genotype, lacking protein expression.
Deletion of the protein in the germline using EIIa-cre or nestin-cre transgenic mice results in viable and fertile heterozyous mice with no obvious histological abnormalities up to a year of age. Homozygous knockout mice are born at a frequency that is 2-fold lower than predicted by Mendelian ratios and have compromised fertility. Both male and female homozygous knockout mice are approximately 25% smaller than wildtype and heterozygous littermates.
Exons 5 and 6 were flanked by loxP sites in (C57BL/6 x 129S4/SvJae)F1-derived V6.5 embryonic stem (ES) cells. The targeting construct contained a floxed neomycin cassette which was removed by transient Cre expression. Resultant mice were established on an FVB genetic background then backcrossed to C57BL/6 for 8 generations by the donating lab.
|Allele Name||targeted mutation 1.1, Ronald DePinho|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Hdac2, histone deacetylase 2|
|Strain of Origin||(C57BL/6 x 129S4/SvJae)F1|
|Molecular Note||LoxP sites were inserted upstream of exon 5 and downstream of exon 6. Protein expression was unaffected as determined by immunoblot analysis of embryonic fibroblasts. Cre-mediated recombination removed the drug selection cassette.|
Heterozygous and homozygous floxed mice are viable and fertile.
When using the B6.Cg-Hdac2tm1.1Rdp/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022625 in your Materials and Methods section.