B6.129X1-Ppargc1b^tm1.1Dpk/J

Stock number: 012378
Research areas: Metabolism Research

Description

Mean respiration rates of mitochondria of homozygous Ppargc1b (peroxisome proliferative activated receptor, gamma, coactivator 1 beta) targeted mutant mice are modestly decreased. When combined with a Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) targeted mutation (see Stock No. 009662), compound mutant animals die shortly after birth with small hearts, bradycardia, intermittent heart block and a markedly reduced cardiac output. Compound mutants also exhibit a severe abnormality in the function and density of mitochondria in heart and brown adipose tissue. This strain may be useful in studies of cardiac development and mitochondrial function.

Detailed description

Mean state 3 respiration rates of mitochondria isolated from hind limb muscle of homozygous Ppargc1b (peroxisome proliferative activated receptor, gamma, coactivator 1 beta) targeted mutant mice are modestly decreased. Electron microscopic analysis of brown adipose tissue does not reveal any significant abnormalities in mitochondrial volume, density, or ultrastructure. When subjected to short-term cold exposure, homozygotes are unable to maintain core body temperature to the same extent as wildtype controls. Homozygotes are born at slightly reduced rates from heterozygous crosses (reported as ~17%), but appear normal. No significant phenotype is observed under non-stressed conditions, and heart function is normal.

When combined with a Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) targeted mutation (see Stock No. 009662), compound mutant animals die shortly after birth with small hearts, bradycardia, intermittent heart block and a markedly reduced cardiac output. Compound mutants also exhibit a severe abnormality in the function and density of mitochondria in heart and brown adipose tissue.

This strain may be useful in studies of cardiac development and mitochondrial function.

Development

A loxP-flanked neomycin resistance cassette was introduced into intron 3 and a third loxP site was placed in intron 6 in 129X1Sv/J-derived SCC10 embryonic stem (ES) cells. Resultant female mice were crossed with a male EIIa-cre animal to excise exons 4-6. This strain was backcrossed to C57BL/6 for 12 generations by the donating laboratory.

Allele

Symbol: Ppargc1b^tm1.1Dpk
Name: targeted mutation 1.1, Daniel P Kelly
MGI accession ID: MGI:3802519
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: PGC-1beta^-
Marker symbol: Ppargc1b
Marker name: peroxisome proliferative activated receptor, gamma, coactivator 1 beta
Marker synonyms: 4631412G21Rik; ERRL1; PERC; PGC-1(beta); PGC1B; PGC1beta; PGC-1beta/ERRL1
Chromosome: 18
Strain of origin: 129X1/SvJ
Molecular note: Germ line, cre-mediated recombination was used to remove exons 4 through 6. Removal of these exons results in a frame shift and a premature STOP codon in exon 7. The absence of protein product was confirmed by western blot analysis on heart extracts.