Gene structure and expression of serotonin receptor HTR2Cin hypothalamic samples from infanticidal and control sows

Claire R Quilter,Meenashki Bagga,Carole A Sargent,Fatima Junaid,Ahmad Moinie

doi:10.1186/1471-2202-13-37

Claire R Quilter, Meenashki Bagga + Show 3 more

Open Access

https://doi.org/10.1186/1471-2202-13-37

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Abstract

BackgroundThe serotonin pathways have been implicated in behavioural phenotypes in a number of species, including human, rat, mouse, dog and chicken. Components of the pathways, including the receptors, are major targets for drugs used to treat a variety of physiological and psychiatric conditions in humans. In our previous studies we have identified genetic loci potentially contributing to maternal infanticide in pigs, which includes a locus on the porcine X chromosome long arm. The serotonin receptor HTR2C maps to this region, and is therefore an attractive candidate for further study based on its function and its position in the genome.ResultsIn this paper we describe the structure of the major transcripts produced from the porcine HTR2C locus using cDNA prepared from porcine hypothalamic and pooled total brain samples. We have confirmed conservation of sites altered by RNA editing in other mammalian species, and identified polymorphisms in the gene sequence. Finally, we have analysed expression and editing of HTR2C in hypothalamus samples from infanticidal and control animals.ConclusionsThe results confirm that although the expression of the long transcriptional variant of HTR2C is raised in infanticidal animals, the overall patterns of editing in the hypothalamus are similar between the two states.Sequences associated with the cDNA and genomic structures of HTR2C reported in this paper are deposited in GenBank under accession numbers FR720593, FR720594 and FR744452.

Highlights

The serotonin pathways have been implicated in behavioural phenotypes in a number of species, including human, rat, mouse, dog and chicken
The best understood activities of hydroxytryptamine (serotonin) receptor 2C (HTR2C) are those elicited via activation of phospholipase C (PLC), there is evidence that other signalling cascades such as phospholipase D and A2 pathways can be stimulated [3]
Polymorphism The in silico analysis combined with the genomic PCR and cDNA PCR experiments confirm that the porcine gene has a similar structure to the human gene, with conservation of the three non-coding 5’UTR exons and all four of the exons encoding the serotonin receptor and 3’ UTR at the genomic level

Summary

Introduction

The serotonin pathways have been implicated in behavioural phenotypes in a number of species, including human, rat, mouse, dog and chicken. An additional level of protein regulation occurs through a cryptic internal splice site in the third coding exon which results in premature termination of the open reading frame In rodents, both the splice junction usage and the mRNA editing are thought to be regulated via non-coding RNAs. In particular the snoRNAs of the Snord115 locus, syntenic with the Prader-Willi Syndrome locus on human chromosome 15 [9], is implicated in mouse models [10,11]. The role of the syntenic locus in humans has been controversial, and more recent analyses have revealed mir-22 as a regulator of HTR2C mRNA expression, and of other candidate genes for panic disorder [12] This latter study does not report which isoform(s) of the transcripts are affected. Detailed sequencing analysis of the extent of editing in the mouse brain confirms that it varies according to the stage of development from the embryo through to the adult [14]: the regulatory mechanisms are highly responsive both spatially and temporally

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