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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.

Original publication

DOI

10.1093/cercor/bhu196

Type

Journal article

Journal

Cereb Cortex

Publication Date

10/2015

Volume

25

Pages

3572 - 3585

Keywords

evolutionary conservation, knockout mouse, noncoding RNA, olfactory bulb, subventricular zone, Animals, Anxiety, Base Sequence, Behavior, Animal, Brain, Conserved Sequence, Evolution, Molecular, Female, Male, Maze Learning, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Phenotype, RNA, Long Noncoding