Role of a neuronal small non-messenger RNA: behavioural alterations in BC1 RNA-deleted mice

Abstract

BC1 RNA is a small non-messenger RNA common in dendritic microdomains of neurons in rodents. In order to investigate its possible role in learning and behaviour, we compared controls and knockout mice from three independent founder lines established from separate embryonic stem cells. Mutant mice were healthy with normal brain morphology and appeared to have no neurological deficits. A series of tests for exploration and spatial memory was carried out in three different laboratories. The tests were chosen as to ensure that different aspects of spatial memory and exploration could be separated and that possible effects of confounding variables could be minimised. Exploration was studied in a barrier test, in an open-field test, and in an elevated plus-maze test. Spatial memory was investigated in a Barnes maze and in a Morris water maze (memory for a single location), in a multiple T-maze and in a complex alley maze (route learning), and in a radial maze (working memory). In addition to these laboratory tasks, exploratory behaviour and spatial memory were assessed under semi-naturalistic conditions in a large outdoor pen. The combined results indicate that BC1 RNA-deficient animals show behavioural changes best interpreted in terms of reduced exploration and increased anxiety. In contrast, spatial memory was not affected. In the outdoor pen, the survival rates of BC1-depleted mice were lower than in controls. Thus, we conclude that the neuron-specific non-messenger BC1 RNA contributes to the aptive modulation of behaviour.

The Brain Cytoplasmic RNA BC1 Regulates Dopamine D2Receptor-Mediated Transmission in the Striatum

“…Striatal dysfunction might contribute to explain the reduced exploration and increased anxiety observed in BC1-KO mice (Lewejohann et al, 2004), because both behavioral aspects involve striatal neuron network (Sareen et al, 2007). In particular, the increased inhibition of GABA transmission in BC1-KO mice could directly explain their increased anxiety, as reported previously for other mouse models (Kash et al, 1999).…”

“…Since its evolutionary conservation with alanine tRNA (Rozhdestvensky et al, 2001), BC1 has been hypothesized to be involved in mRNA translation. BC1 knock-out (KO) mice have been generated recently (Skryabin et al, 2003) and showed reduced exploration and increased anxiety (Lewejohann et al, 2004).…”

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

“…Snora35 gene-depleted mice do not appear to display a phenotype different from their wild-type siblings, thus far (BV Skryabin and J Brosius, unpubl.). In another example of an RNA knockout, it took several years of work to tease out a reduced exploratory behavior in mice when small cytoplasmic BC1 RNA, phylogenetically restricted to rodents and expressed in neurons where it is delivered to dendritic processes, was deleted (Tiedge et al 1991;Martignetti and Brosius 1993;Lewejohann et al 2004). In a further mouse snoRNA knockout, the entire cluster encoding Snord116 RNA isoforms (earlier termed MBII-85 snoRNA) was deleted from a locus associated with Prader-Willi syndrome, a neurodevelopmental disorder in humans.…”

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

“…Interestingly, BC1 RNA is specifi-cally targeted to dendritic domains in neurons (Tiedge et al 1991). BC1 knockout mice show behavioral changes and lower survival rates as compared with normal controls (Lewejohann et al 2004). BC1 RNA has been found to interact with the Fragile X mental retardation protein (FMRP).…”