Gad2 knock-out mice exhibit stress-generated seizures, but homozygous-null mice on this NOD.129 background exhibit a higher incidence of apparently less severe seizures than mice with this knock-out on a B6.129 background. They are suitable for use in applications related to the study of epilepsy.
Steinunn Baekkeskov, UCSF
Gad2-null mice are viable and fertile. Gross appearance is similar to wildtype littermates; brain weight is unaffected, as is cytoarchitecture. Starting as early as 12 weeks of age, homozygous-null mice develop stress-generated seizures induced by cage lid removal and other routine handling. This epileptic syndrome results in increased mortality.
Other phenotypic observations
* defect in the plastcicity of the visual cortex during development
* increased anxiety-like responses in open field and elevated zero maze assays
* diminished response to anxiolytics (anti-anxiety agents)
* Defect in the ability to sustain maximum gamma-aminobutyric acid release during stimulation
Genetic background influences this strain's phenotype. Homozygous-null mice on a mixed NOD,129 background exhibit a higher incidence of apparently less severe seizures than mice on a B6,129 background (also see Stock No. 003654).
Exon 1 is disrupted in this strain. A targeting vector containing the neomycin resistance gene under the control of the phosphoglycerol kinase promoter was introduced into the BamHI site in exon 1 just downstream of the transcription and translation start sites. The construct was electroporated into 129X1/SvJ-derived JM1 embryonic stem cells and selected cells were injected into C57BL/6 blastocysts. No protein product was detected in brain extracts of homozygous-null mice using Western blots.
|Allele Name||targeted mutation 1, Steinunn Baekkeskov|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||GAD 65 (-); GAD65 -|
|Gene Symbol and Name||Gad2, glutamic acid decarboxylase 2|
|Strain of Origin||129X1/SvJ|
|General Note||Phenotypic Similarity to Human Syndrome: Epilepsy (J:44638).|
|Molecular Note||A neomycin resistance cassette was inserted into exon 1, downstream of the translation initiation start site. Western blot analysis on brain extracts from homozygous mice confirmed that no detectable protein is expressed from this allele.|
|Mutations Made By|| |
Steinunn Baekkeskov, UCSF
This strain originated on a B6,129 background. It is maintained as a heterozygote on a NOD/LtJ background.
When using the NOD-GAD65- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003653 in your Materials and Methods section.