B6.Cg-Tfam^tm1.1Ncdl/J

Stock number: 026123
Research areas: Cell Biology Research, Research Tools

Description

Tfam^fl/fl floxed mice may be useful for studying the effect of mitochondrial genome instability on human diseases.

Detailed description

Tfam^fl/fl floxed mice possess loxP sites flanking exons 6-7 of the transcription factor A, mitochondrial (Tfam) gene. TFAM is required for the transcription of mitochondrial (mt)DNA encoding electron transport chain subunits. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 6-7 deleted in cre-expressing tissues.

For example, when crossed to B6N.FVB-Tg(ACTB-cre)2Mrt/CjDswJ mice (Stock No. 019099) with widespread expression of Cre recombinase, Tfam^+/- mice have 30% to 50% depletion on mtDNA in tissues, with normal amounts of mtDNA transcripts and increased oxidative mtDNA damage. When further crossed to mice susceptible to spontaneous intestinal adenomas, C57BL/6J-Apc^Min/J (Stock No. 002020), resulting mice exhibit increased tumor number and growth in the small intestine.

Development

A targeting vector was designed to insert a loxP site upstream of exon 6, and a frt-flanked neomycin resistance (neo) cassette followed by a single loxP site downstream of exon 7 of the transcription factor A, mitochondrial (Tfam) gene. The construct was electroporated into B6(Cg)-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with C57BL/6J females. Resulting Tfam^fl/fl were bred C57BL/6J mice before being bred to B6.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/RainJ (Stock No. 009086) mice to remove the neo. These mice were crossed to remove the FLP-expressing transgene. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Tfam^tm1.1Ncdl
Name: targeted mutation 1.1, Navdeep Chandel
MGI accession ID: MGI:5586702
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Tfam
Marker name: transcription factor A, mitochondrial
Chromosome: 10
Strain of origin: B6.Cg-Thy1^a
Molecular note: A targeting vector was designed to insert a loxP site upstream of exon 6, and a FRT-flanked neomycin resistance (neo) cassette followed by a single loxP site downstream of exon 7 of the gene. Flp mediated recombination removed the neomycin cassette.