When f/f-Fos mice are crossed with D1-Cre mice resulting offspring have exons 3-4 deleted in dopamine D1 receptor-expressing neurons. Fos D1 receptor deleted mice exhibit altered behavioral sensitization to repeated cocaine administration and may be useful for studying cocaine-induced neuroadaptation in dopamine pathways.
Ming Xu, University of Chicago
Fos (FBJ osteosarcoma oncogene) encodes a leucine zipper protein that in combination with with JUN family proteins forms the AP-1 transcription factor complex. Fos is involved in the regulation of cell proliferation, differentiation and transformation.
f/f-Fos mice possess loxP sites flanking exons 3-4 and are viable and fertile. When combined with mice carrying the Tg(Drd1a-cre)120Mxu (D1-Cre) transgene, Fos expression is eliminated in dopamine D1 receptor-expressing neurons.
f/f-Fos-D1-Cre mice do not exhibit increased locomotion, sensitized rearing, or increases in dendritic branching and dendritic spine density in medium spiny neurons following chronic cocaine administration. Mutant mice tested for conditioned place preference (CPP) are slower to show extinction of CPP behaviors, exhibiting a more persistent memory of the reinforcing effects of cocaine. This strain may be useful for studying cocaine-induced neuroadaptation in dopamine pathways.
A targeting vector was designed to flank exons 3 and 4 and a neomycin cassette placed downstream of exon 4 with loxP sites, a region which encodes the DNA binding domain and leucine zipper domain needed for heteordimerization with JUN family proteins. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeras were bred to C57BL/6 mice. Mice were then bred to mice carrying the Tg(Drd1a-cre)120Mxu transgene on a C57BL/6 background.
Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice for at least one generation to establish the colony. The Tg(Drd1a-cre)120Mxu transgene was bred out of this strain and is maintained separately as MMRRC #037156.
|Allele Name||targeted mutation 1, Ming Xu|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Fos, FBJ osteosarcoma oncogene|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A region containing sequence encoding the DNA-binding and leucine zipper domains and a downstream neo transgene was flanked by single loxP sites. In situ hybridization and immunostaining indicated that the loxP sites did not interfere with transcription or translation.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the f/f c-fos mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37115 in your Materials and Methods section.
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