Cloning and tissue distribution of novel splice variants of the ovine ghrelin gene

Abstract

BackgroundThe ghrelin axis is involved in the regulation of metabolism, energy balance, and the immune, cardiovascular and reproductive systems. The manipulation of this axis has potential for improving economically valuable traits in production animals, and polymorphisms in the ghrelin (GHRL) and ghrelin receptor (GHSR) genes have been associated with growth and carcass traits. Here we investigate the structure and expression of the ghrelin gene (GHRL) in sheep, Ovis aries.ResultsWe identify two ghrelin mRNA isoforms, which we have designated Δex2 preproghrelin and Δex2,3 preproghrelin. Expression of Δex2,3 preproghrelin is likely to be restricted to ruminants, and would encode truncated ghrelin and a novel C-terminal peptide. Both Δex2 preproghrelin and canonical preproghrelin mRNA isoforms were expressed in a range of tissues. Expression of the Δex2,3 preproghrelin isoform, however, was restricted to white blood cells (WBC; where the wild-type preproghrelin isoform is not co-expressed), and gastrointestinal tissues. Expression of Δex2 preproghrelin and Δex2,3 preproghrelin mRNA was elevated in white blood cells in response to parasitic worm (helminth) infection in genetically susceptible sheep, but not in resistant sheep.ConclusionsThe restricted expression of the novel preproghrelin variants and their distinct WBC expression pattern during parasite infection may indicate a novel link between the ghrelin axis and metabolic and immune function in ruminants.

Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide

“…Indeed, the removal of exon 2 from putative preproghrelin mRNAs of all species examined allows the retention of the cognate preproghrelin reading frame. We recently described an exon 2-deleted ghrelin splice variant in mice and sheep [ 17 ]. The canonical human preproghrelin coding sequence consists of 117 amino acids (AAs).…”

“…AB111891) and sheep (GenBank accession no. KF219676) [ 17 ]. In1-ghrelin and exon 2-deleted preproghrelin transcripts are present in humans and mice, which represents conservation spanning at least 90 million years.…”

“…The in1-ghrelin transcript contains exon 1, intron 1 and exon 2, and the inclusion of intron 1 leads to a truncation of the ghrelin peptide sequence [ 15 ]. We recently reported an exon 2-deleted splice variant in mouse and sheep [ 17 ]. In this study, we sought to determine whether any ghrelin gene-derived splice variants are conserved across vertebrates and present preliminary findings on the function of splice variants encoding derived short, C-terminally truncated ghrelin peptides (here termed minighrelin).…”

Gastrointestinal Spatiotemporal mRNA Expression of Ghrelin vs Growth Hormone Receptor and New Growth Yield Machine Learning Model Based on Perturbation Theory

“…The GHR has also been widely studied in ruminants, and it has been suggested as a preferential target for genetic breeding because it is significantly associated with growth traits, such as milk yield, meat production and growth 21 22 23 24 . As stated in a previous study 25 , the Ghrelin pathway (which includes Ghrelin, GHSR-1a, and ghrelin-O-acyl transferase) is a potential target for the improvement of ruminants’ production. This could be achieved through the modification of feeding behavior, body composition, immune and reproductive functions.…”

Ghrelin and NUCB2/Nesfatin‐1 Co‐Localization With Digestive Enzymes in the Intestine of Pejerrey (Odontesthes bonariensis)

“…The gut shows the highest expression of preproghrelin mRNA in both mammals (Menzies et al ., ) and fish (Sánchez‐Bretaño et al ., ; Volkoff, ). Besides, the presence of the ghrelin peptide has been reported in the intestine of several fish species, including rainbow trout (Sakata et al ., ), Japanese eel (Kaiya et al ., ), goldfish (Kerbel and Unniappan, ), and zebrafish (Olsson et al ., ).…”