These Gabrd knock-out mice exhibit exhibit a decreased sensitivity to the sedative/hypnotic, anxiolytic and pro-absence effects of neuroactive steroids.
Gregg E Homanics, University of Pittsburgh
Mice that are homozygous null for Gabrd are viable and fertile. Northern blot analysis of -/- adult cerebellar RNA suggests that a chimeric Gabrd/neo transcript is generated from the targeted allele. Western blot analysis fails to detect a Gabrd protein product. Maximal binding for the agonist muscimol was markedly decreased in whole brain homogenates. Consistent with this, in situ autoradiographic analysis indicates a drastic reduction in muscimol binding in most parts of the brain. In general, these mice exhibit a decreased sensitivity to the sedative/hypnotic, anxiolytic and pro-absence effects of neuroactive steroids as determined by sleep time assays, elevated plus-maze assays (measures anxiolytic effect) and the inability of neuroactive steroids to prolong pentylenetetrazol-induced seizures. This decreased sensitivity appears to be selective however, as differential responses to various neuroactive steroids are observed.
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).
A replacement-type DNA targeting vector containing a MC1Neo gene was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 ES cells. The construct was designed to disrupt exon 4. Selected ES cells were isolated and injected into C57BL/6J blastocysts. Chimeric males were mated to C57BL/6J females. Mice have been backcrossed to C57BL/6J for ten generations.
|Allele Name||targeted mutation 1, Gregg E Homanics|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||delta-; delta0|
|Gene Symbol and Name||Gabrd, gamma-aminobutyric acid (GABA) A receptor, subunit delta|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Insertion of a MC1-neomycin resistance cassette into exon 4 disrupted the gene. Northern blot analysis of cerebellar total RNA from homozygous mutant adult mice detected moderate levels of a novel 2.3kb transcript but not the 1.9kb wild-type transcript. Western blot analysis of cerebellar membranes did not detect the wild-type protein in homozygous mutant mice.|
|Mutations Made By|| |
Gregg Homanics, University of Pittsburgh
When maintaining a live colony, homozygous mice may be bred together.
When using the delta0 mouse strain in a publication, please cite the originating article(s) and include JAX stock #003725 in your Materials and Methods section.