These Gabrg2 knock-out mice exhibit increased levels of anxiety; they also show longer sleep time in response to midazolam and zolpidem. They are suitable for use in applications related to the role of GABAergic transmission in diverse behavioral activities.
Gregg E Homanics, University of Pittsburgh
The gamma subunit of the gamma aminobutyric acid type A receptor is essential for bestowing both normal single channel conductance and sensitivity to benzoidiazepines. Alternate RNA splicing produces two alternative forms of the gamma2 subunit from Gabrg2. The two forms, gamma2L and gamma2S are expressed in different brain regions. This strain is a knockout of the gamma2L form. Mice homozygous for this exon deletion are viable and superficially indistinguishable from wildtype mice. Behaviorally, gamma2L knockout mice show increased levels of anxiety in the elevated plus maze relative to controls and also longer sleep time than control mice in response to midazolam and zolpidem. Female fertility is normal, but heterozygous male fertility is reduced (about 16% of heterozygous males are fertile).
Of note, several strains bearing gamma-aminobutyric acid (GABA-A) receptor mutations are available from this donating investigator (Dr. Gregg Homanics, University of Pittsburgh), including Gabra1 (Stock No. 004318), Gabra4 (Stock No. 006874), Gabra6 (Stock No. 002710), Gabrb3 (Stock No. 002711), Gabrd (Stock No. 003725), and Gabrg2 (Stock No. 003137).
The knockout was created through the replacement of a 0.6 kb XbaI fragment which includes the 24 bp exon 9 and associated splice signals with the bicistronic selectable marker gene (PGKneoNTRtkpA). The 129X1/SvJ x 129S1/Sv-derived ES (embryonic stem) cell line was used. It is currently on a B6,129 background.
|Allele Name||targeted mutation 1, Gregg E Homanics|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Gabrg2, gamma-aminobutyric acid (GABA) A receptor, subunit gamma 2|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A neomycin selection cassette replaced a genomic fragment containing exon 9. RT-PCR experiments demonstrated that this mutation resulted in the elimination of the expression of the long splice variant but not the short splice variant. Radioligand binding assays confirmed that no functional long variant was expressed from this allele.|
|Mutations Made By|| |
Gregg Homanics, University of Pittsburgh
When maintaining a live colony, heterozygous or homozygous females may be bred with heterozygous males. Female fertility is normal, but heterozygous male fertility is reduced (about 16% of heterozygous males are fertile). The expected coat color from breeding is black.
When using the γ2L- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003137 in your Materials and Methods section.