This Liastm1Mae mutant allele has the exons 4-6 of the of the lipoic acid synthetase (Lias) gene deleted. The deleted region encodes the functionally conserved Cys motifs of the enzyme responsible for converting octanoic acid to α-lipoic acid (also called 1,2-dithiolane-3-pentanoic acid, thioctic acid, ALA, or LA). These Lias mutant mice may be useful in studying α-lipoic acid requirements during development, mitochondrial dysfunction, and oxidative stress-related diseases such as diabetes, atherosclerosis, and neurodegenerative disorders.
Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Lias | lipoic acid synthetase |
The Liastm1Mae mutant allele has the exons 4-6 of the of the lipoic acid synthetase (Lias) gene deleted. The deleted region encodes the functionally conserved Cys motifs of the enzyme responsible for converting octanoic acid to α-lipoic acid (also called 1,2-dithiolane-3-pentanoic acid, thioctic acid, ALA, or LA) via insertion of a sulfur atom into the hydrocarbon chain of octanoic acid. Lias mRNA expression in heterozygous mice is approximately half of wildtype levels. Lias homozygous mice die in utero shortly after implantation. When heterozygous dams are fed an exogenous racemic α-lipoic acid diet (equal amounts of left- and right-handed enantiomers of the chiral α-lipoic acid molecule), embryonic lethality of homozygous embryos is not rescued. Heterozygous mice are viable and fertile, with a mild reduction of plasma antioxidant capacity. Inducing stress conditions (such as inflammation, hypercholesterolemia and hyperglycemia) is expected to result in significantly reduced endogenous antioxidant capacity. Specifically, heterozygous mice exhibit significantly increased reactive oxygen species (ROS) levels following lipopolysaccharide-induced sepsis. In addition, heterozygous Lias-deficiency enhances atherosclerosis in apoE-deficient male mice (see details below). These Lias mutant mice may be useful in studying α-lipoic acid requirements during development, mitochondrial dysfunction, and oxidative stress-related diseases such as diabetes, atherosclerosis, and neurodegenerative disorders.
When 129S6-Lias mutant mice are bred with 129S6-apoE mutant mice
(Stock No. 014556), enhanced atherosclerosis and reduced antioxidant capacity is observed in males heterozygous for the Lias mutation and homozygous for the apoE mutation (129S6-Lias+/-apoE-/-). Compared to 129S6-apoE-/- males, 129S6-Lias+/-apoE-/- males have significantly larger atherosclerotic lesions at the aortic sinus accompanied by enhanced oxidative stress, increased plasma cholesterol, and a transition from glucose to lipid catabolism in the liver (reduced pyruvate dehydrogenase complex activity). 129S6-Lias+/-apoE-/- males have significant reductions in aortic expression of antioxidant enzyme genes (including superoxide dismutase 1 and 2 (SOD1 and SOD2)) compared to 129S6-apoE-/- males.
A targeting vector was designed in the laboratory of Dr. Nobuyo Maeda (University of North Carolina at Chapel Hill) to replace exons 4-6 of the lipoic acid synthetase (Lias) gene with a reverse-oriented neomycin resistance cassette. The deleted ~3.7 kbp region encodes the functionally conserved Cys motifs of the enzyme responsible for converting octanoic acid to α-lipoic acid (also called 1,2-dithiolane-3-pentanoic acid, thioctic acid, ALA, or LA) via insertion of a sulfur atom into the hydrocarbon chain of octanoic acid. To generate mutant mice on a 129S6/SvEv genetic background, the construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with 129S6/SvEvTac females to establish the colony. Mice heterozygous for the Liastm1Mae mutant allele were maintained on a 129S6/SvEvTac genetic background prior to sending to The Jackson Laboratory Repository. Upon arrival, mutant mice were maintained on the 129S6/SvEvTac genetic background by breeding heterozygous mice with wildtype mice from the colony.
Allele Name | targeted mutation 1, Nobuyo Maeda |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Lias- |
Gene Symbol and Name | Lias, lipoic acid synthetase |
Gene Synonym(s) | |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 5 |
Molecular Note | A 3.7 kb sequence including exons 4-6 was replaced by a neomycin resistance gene. The deleted sequence encoded the functionally conserved Cys motifs, and loss of it resulted in a null allele. |
Mutations Made By | Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill |
When maintaining a live colony, heterozygous mice may be bred together or to wildtype mice from the colony. Homozygous knockout mice die in utero shortly after implantation.
When using the 129S6/SvEv-Liastm1Mae/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013046 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Lias<tm1Mae> |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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.