These LiasLow hypomorph mice under express lipoic acid synthetase. These mice may be suitable for use in studies related to oxidative stress and the role of antioxidants in disease.Read More +
The targeted Lias gene encodes a lipoic acid synthetase that is critical in synthesis of alpha-lipoic acid. These LiasHigh mice carry a hypomorph allele of Lias gene, with cFos gene 3'-UTR sequence directing expression of the endogenous Lias.
Homozygous LiasLow mice have unstabilized Lias transcripts resulting in reduced expression and LIAS protein levels approximately 25% compared to levels in wildtype mice, as assessed by Western blot analysis of kidney tissue.
When crossed with C57BL/6-Ins2Akita/J mice (Stock No. 003548) the resulting double mutant mice exhibit more severe diabetic nephropathy features and higher oxidative stress when compared to the single mutant C57BL/6-Ins2Akita/J mice.
A targeting vector designed by Dr. Nobuyo Maeda (University of North Carolina, Chapel Hill) containing
loxP site flanked bovine growth hormone gene 3’-UTR sequence and a NEO cassette, and 3’-UTR sequence of the cFos gene was inserted into the 3’-UTR of the Lias gene. The construct was electroporated into C57BL/6N derived Chemicon B/6N embryonic stem (ES) cells at The Jackson Laboratory. Correctly targeted ES cells were injected into albino C57BL/6J blastocysts. The resulting chimeric mice were crossed to C57BL/6J (Stock No. 000664). LiasHigh (LiasH) heterozygotes were crossed to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J (Stock No. 003724) mice to excise the floxed bovine growth hormone gene 3’-UTR sequence and a NEO cassette. The resulting LiasLow mice were bred to C57BL/6J to remove the transgene. Sperm was cryopreserved.
|Allele Name||targeted mutation 2.1, Nobuyo Maeda|
|Allele Type||Targeted (Hypomorph)|
|Gene Symbol and Name||Lias, lipoic acid synthetase|
|Strain of Origin||C57BL/6N|
|General Note||ES cell line - Chemicon B/6N|
|Molecular Note||The targeting vector consists of a loxP site, the 3' UTR sequence of the bovine growth hormone gene, a neomycin cassette and a loxP site followed by the 3'-UTR sequence of the cFos gene. Cre-mediated recombination removed the bovine growth hormone gene and neo cassette, allowing cFos to drive expression of the endogenous gene. Expression is 25% of the endogenous gene expression.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the LiasLow mouse strain in a publication, please cite the originating article(s) and include JAX stock #008350 in your Materials and Methods section.