title: Genetically-directed Sparse Neuronal Labeling in BAC Transgenic Mice through Mononucleotide Repeat Frameshift.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: X William
authors.initials: XW
authors.lastname: Yang
mesh_terms: D000818:Animals; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D016368:Frameshift Mutation; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D013131:Spine / Q000378:metabolism / Q000473:pathology
chemical_list: D017447:Receptors, Dopamine D1