This strain is currently unavailable due to replenishing of cryopreserved stocks. Interested customers can register interest.
Aldh5a1 knockout mice may be useful in studying succinate semialdehyde dehydrogenase (SSADH) deficiency and to explore the effect of GABA and GHB accumulation on central nervous system development and function.
Michael Gibson, Children's Hospital Pittsburgh
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Aldh5a1 | aldhehyde dehydrogenase family 5, subfamily A1 |
Mice homozygous for the Aldh5a1 knockout exhibit reduced body weight, ataxia, seizures, gliosis of the hippocampus, and eventual status epilepticus. From 19-26 days of age, repetitive tonic-clonic seizures results in more than 95% mortality. Biochemical assays shows complete ablation of the endogenous enzymatic activity in the brains, livers, hearts, and kidneys of homozygous mutant mice. Homozygotes have increased levels of GHB and GABA in liver and brain tissues, as well as in urine. Phenotype can be rescued to varying degrees utilizing a number of both pharmacotherapeutic and gene therapeutic approaches. Although heterozygous mice have approximately 50% of the endogenous enzyme activity compared to wildtype mice, they are viable and fertile. Mice with this targeted mutation may be useful in studying succinate semialdehyde dehydrogenase (SSADH) deficiency and to explore the effect of GABA and GHB accumulation on central nervous system development and function.
A targeting vector was designed to replace the 844 bp fragment (containing most of exon 7 and a large part of the active site) of the endogenous gene with a PGK-neo cassette. This construct was electroporated into "129/SV"-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric males were bred to C57BL/6 females. Heterozygous mice were backcrossed to C57BL/6 for at least ten generations prior to arrival at The Jackson Laboratory.
Allele Name | targeted mutation 1, K Michael Gibson |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Aldh5a1-; SSADH-; SSADH-deficient |
Gene Symbol and Name | Aldh5a1, aldhehyde dehydrogenase family 5, subfamily A1 |
Gene Synonym(s) | |
Strain of Origin | 129/Sv |
Chromosome | 13 |
Molecular Note | A 1.65-kb neomycin cassette was used to replace 844 nucleotides comprising most of exon 7 and encoding the active site of the protein. Biochemical assays confirmed the ablation of enzymatic activity in the brains, livers, hearts, and kidneys of homozygous mutant mice. |
Mutations Made By | Michael Gibson, Children's Hospital Pittsburgh |
When maintaining a live colony, heterozygous mice are bred. Homozygous mice will die around three weeks of age with seizures.
When using the B6.129-Aldh5a1tm1Kmg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006257 in your Materials and Methods section.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.