title: Disruption of Visc-2, a Brain-Expressed Conserved Long Noncoding RNA, Does Not Elicit an Overt Anatomical or Behavioral Phenotype.
abstract: Although long noncoding RNAs (lncRNAs) are proposed to play essential roles in mammalian neurodevelopment, we know little of their functions from their disruption in vivo. Combining evidence for evolutionary constraint and conserved expression data, we previously identified candidate lncRNAs that might play important and conserved roles in brain function. Here, we demonstrate that the sequence and neuronal transcription of lncRNAs transcribed from the previously uncharacterized Visc locus are conserved across diverse mammals. Consequently, one of these lncRNAs, Visc-2, was selected for targeted deletion in the mouse, and knockout animals were subjected to an extremely detailed anatomical and behavioral characterization. Despite a neurodevelopmental expression pattern of Visc-2 that is highly localized to the cortex and sites of neurogenesis, anomalies in neither cytoarchitecture nor neuroproliferation were identified in knockout mice. In addition, no abnormal motor, sensory, anxiety, or cognitive behavioral phenotypes were observed. These results are important because they contribute to a growing body of evidence that lncRNA loci contribute on average far less to brain and biological functions than protein-coding loci. A high-throughput knockout program focussing on lncRNAs, similar to that currently underway for protein-coding genes, will be required to establish the distribution of their organismal functions.
authors.affiliation: MRC Functional Genomics Unit Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Oliver
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK Genome Technology Branch.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Chodroff
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Amrit
authors.initials: A
authors.lastname: Gosal
authors.affiliation: MRC Functional Genomics Unit.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Edwards
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Amanda F P
authors.initials: AF
authors.lastname: Cheung
authors.affiliation: Embryonic Stem Cells and Transgenic Mouse Core, National Human Genome Research Institute, Bethesda, MD 20892, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Gomez-Rodriguez
authors.affiliation: Embryonic Stem Cells and Transgenic Mouse Core, National Human Genome Research Institute, Bethesda, MD 20892, USA.
authors.forename: Gene
authors.initials: G
authors.lastname: Elliot
authors.affiliation: Embryonic Stem Cells and Transgenic Mouse Core, National Human Genome Research Institute, Bethesda, MD 20892, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Garrett
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Lickiss
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Francis
authors.initials: F
authors.lastname: Szele
authors.affiliation: Genome Technology Branch.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Molnár
authors.affiliation: MRC Functional Genomics Unit Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; C000608708:Visc-2 long non-coding RNA, mouse
keywords: evolutionary conservation; knockout mouse; noncoding RNA; olfactory bulb; subventricular zone