C57BL/6-Lias^tm2Mae/1J

Stock number: 008348
Product name: Lias^High
Strain synonyms: hypermorphic Lias mice
Research areas: Diabetes and Obesity Research, Research Tools

Description

These Lias^High mice overexpress 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 hypermorph allele of Lias gene, with bovine growth hormone gene 3’-UTR sequence directing expression of the endogenous Lias. Homozygous Lias^High mice have stabilized Lias transcripts resulting in overexpression and LIAS protein levels approximately150% compared to levels in wildtype mice, as assessed by Western blot analysis of kidney tissue. The bovine growth hormone gene 3’-UTR sequence is flanked by loxP sites: when crossed to a strain expressing Cre recombinase, the bovine growth hormone gene 3’-UTR sequence is excised and expression of Lias is controlled by the cFos gene 3”-UTR.

When crossed with C57BL/6-Ins2^Akita/J mice (Stock No. 003548) the resulting double mutant mice exhibit less severe diabetic nephropathy and lower 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). The Lias^H (high) colony was maintained on the C57BL/6J background and cryopreserved as sperm.

Allele

Symbol: Lias^tm2Mae
Name: targeted mutation 2, Nobuyo Maeda
MGI accession ID: MGI:5810125
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
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. The bovine growth hormone gene 3'-UTR sequence directs expression of the endogenous Lias creating a hypermorph allele. Expression is 150% of endogenous gene expression.
General note: ES cell line - Chemicon B/6N