B6(FVB)-Lias^tm2.1Mae/J

Stock number: 008350
Product name: Lias^Low
Strain synonyms: hypomorphic Lias mice
Research areas: Diabetes and Obesity Research, Research Tools

Description

These Lias^Low 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.

Detailed description

The targeted Lias gene encodes a lipoic acid synthetase that is critical in synthesis of alpha-lipoic acid. These Lias^High mice carry a hypomorph allele of Lias gene, with cFos gene 3'-UTR sequence directing expression of the endogenous Lias. Homozygous Lias^Low 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-Ins2^Akita/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-Ins2^Akita/J mice.

Development

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). Lias^High (Lias^H) 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 Lias^Low mice were bred to C57BL/6J to remove the transgene. Sperm was cryopreserved.

Allele

Symbol: Lias^tm2.1Mae
Name: targeted mutation 2.1, Nobuyo Maeda
MGI accession ID: MGI:5810126
Generation method: Targeted
Attributes: Hypomorph
Marker symbol: Lias
Marker name: lipoic acid synthetase
Chromosome: 5
Strain of origin: C57BL/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.
General note: ES cell line - Chemicon B/6N