Journal
CEREBRAL CORTEX
Volume 25, Issue 10, Pages 3572-3585Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhu196
Keywords
evolutionary conservation; knockout mouse; noncoding RNA; olfactory bulb; subventricular zone
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Funding
- UK Medical Research Council
- Biotechnology and Biological Sciences Research Council, UK
- European Research Council through DARCGENs
- University of Oxford
- BBSRC [BB/I021833/1, BB/F003285/1] Funding Source: UKRI
- MRC [G0900901, MC_U137761446, MC_UU_12021/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F003285/1, BB/I021833/1] Funding Source: researchfish
- Medical Research Council [G0900901, MC_U137761446, MC_UU_12021/1] Funding Source: researchfish
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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.
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