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Conditional knock‐down of the transcriptional coactivator PGC‐1α in mice using Cre‐LoxP induced RNA interference
Author(s) -
Bagattin Alessia,
Hugendubler Lynne,
Hayes Schantel,
Mueller Elisabetta
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1016.8
Subject(s) - coactivator , mitochondrial biogenesis , transgene , genetically modified mouse , gene knockin , biology , rna interference , microbiology and biotechnology , biogenesis , peroxisome proliferator activated receptor , mitochondrion , receptor , transcription factor , gene , rna , genetics
PGC‐1α (peroxisome proliferator‐activated receptor gamma coactivator 1α) is a transcriptional coactivator involved in mitochondrial biogenesis and energy metabolism. The function of PGC‐1α has been studied in vivo through the generation of tissue‐specific transgenic and knock‐out models. We have used RNAi technology to generate transgenic mice with a conditional knock‐down of PGC‐1α in order to study the contribution of PGC‐1α in the response to various metabolic challenges. Mice carrying the U6‐ploxPneo‐PGC‐1α‐RNAi transgene were crossed with EIIa‐Cre transgenic mice to ubiquitously knock‐down PGC‐1α expression in vivo. U6‐PGC‐1α‐EIIa‐Cre mice were born at the expected Mendelian ratio. Upon cold exposure, PGC‐1α knock‐down transgenic mice exhibit reduced PGC‐1α mRNA induction in brown fat compared to controls and, as previously shown in knock‐out mice, they have decreased UCP1 (uncoupling protein 1) mRNA levels. Furthermore, microscopic analysis of H&E stained brown fat tissue sections revealed accumulation of large lipid droplets, as previously observed in PGC‐1α knock‐out animals. In conclusion, we have developed an animal model that mirrors the total PGC‐1α knock‐out mouse and that allows investigation of PGC‐1α function in vivo through a system that does not require the lengthy process of gene‐targeting nor ES cell manipulation. Supported by the Intramural Research Program of NIDDK, NIH.