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Sci Rep. 2017 Mar 8;7:43915. doi: 10.1038/srep43915.

Genetically-directed Sparse Neuronal Labeling in BAC Transgenic Mice through Mononucleotide Repeat Frameshift.

Lu XH1,2, Yang XW1,2.

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Center for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, Los Angeles, CA 90095, USA.
Department of Psychiatry &Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.


Mosaicism with Repeat Frameshift (MORF) allows a single Bacterial Artificial Chromosome (BAC) transgene to direct sparse labeling of genetically-defined neuronal populations in mice. The BAC transgene drives cell-type-specific transcription of an out-of-frame mononucleotide repeat that is placed between a translational start codon and a membrane-bound fluorescent protein lacking its start codon. The stochastic frameshift of the unstable repeat DNA in a subset of BAC-expressing neurons results in the in-frame translation of the reporter protein hence the sparse neuronal labeling. As a proof-of-concept, we generated D1-dopamine receptor (D1) BAC MORF mice that label about 1% striatal D1-expressing medium spiny neurons and allow visualization of their dendrites. These mice enable the study of D1-MSN dendrite development in wildtype mice, and its degeneration in a mouse model of Huntington's disease.

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