B6.129S4-Pparg^tm3(tTA)Yba/J

Stock number: 008227
Research areas: Developmental Biology Research, Metabolism Research, Research Tools

Description

These mice express tTA (tetracycline regulated transactivator) from the endogenous Pparg locus. Heterozygotes exhibit mild lipodystrophy with pale, unilocular brown adipocytes, hypertrophy of brown fat, reduced subcutaneous fat, reduced gonadal fat pads, mild hepatomegaly and develop insulin resistance and dyslipidemia. Treatment with doxycycline prevents this phenotype. This mutant mouse strain may be useful in studies of lipodystrophy.

Detailed description

These mice express tTA (tetracycline regulated transactivator) from the endogenous Pparg locus. A fusion transcript (including the 5' portion of Pparg, IRES and tTA (AF1-IRES-tTA)) and a wild-type Pparg transcript are detected by Northem blot analysis of epididymal fat pads from heterozygotes. Mice that are heterozygous for this targeted mutation exhibit a similar but milder phenotype than that observed in Pparg-Ldi mice (129-Pparg^tm2Yba/J, Stock No. 008079). Heterozygotes exhibit mild lipodystrophy with pale, unilocular brown adipocytes, hypertrophy of brown fat, reduced subcutaneous fat, gonadal fat pads smaller than wild-type and mild hepatomegaly. Mutant mice develop insulin resistance and dyslipidemia. Treatment with doxycycline prevents this phenotype. Mice that are homozygous for the targeted mutation are not viable. This mutant mouse strain may be useful in studies of lipodystrophy.

Development

A targeting vector containing an IRES sequence, tTA (tetracycline regulated transactivator) gene, PGK-neo cassette, and synthetic polyA, was used to replace exon 2. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S1/SvImJ mice, and then backcrossed to C57BL/6J for 7 generations. The Donating Investigator maintained the strain by crossing heterozygote males to wildtype females.

Allele

Symbol: Pparg^tm3(tTA)Yba
Name: targeted mutation 3, Yaacob Barak
MGI accession ID: MGI:3511359
Generation method: Targeted
Attributes: Transactivator
Marker symbol: Pparg
Marker name: peroxisome proliferator activated receptor gamma
Chromosome: 6
Strain of origin: Not Specified
Expressed genes: tTA,tetracycline-controlled transactivator,E. coli
Site of expression: Expression of tTA from the endogenous Pparg locus is detected in adipose tissue.
Molecular note: Exon 2 was replaced with an IRES, tTA and neo cassette. While expression is modest in adipose tissue, it is poor in the liver and placenta.