Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens

Abstract

BackgroundA deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week-old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition.ResultsAt the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down-regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3′ untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines.ConclusionsThere is a critical miRNA, let-7b, involved in the regulation of GHR. SOCS3 plays a critical role in regulating skeletal muscle growth and fat deposition via let-7b-mediated GHR expression.

The Associations of GH and GHR Genes with Carcass Components in Indonesian Kampung and Broiler Chicken Cross

“…Our finding proposed that the GG genotype of the g.565G>A GHR had positive effect on chicken carcass and yielded proportional body composition. The inhibition of normal human and animal skeletal muscle growths and fat depositions was reported to be caused by mutation in GHR gene by causing the inhibition of GH signal transduction (Lin et al, 2012). However, the molecular mechanism of GHR introns and its effect on muscle growth in chicken is unclear.…”

Positive selection rather than relaxation of functional constraint drives the evolution of vision during chicken domestication

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Application of Animal Biomodel using Poultry: A Review

“…이 증후군의 원인은 가족성 왜소증으로 혈청내 GH 수준 은 정상이지만 IGF-1 수치가 낮은 원인이 있는 것을 확인한 바 있다 (Laron et al, 1966). 최근에 유전자 발현에 영향을 주 는 miRNA 연구를 통해 GHR의 let-7b가 주요한 역할을 하고, SOCS3(Suppressor Of Cytokine Signaling 3) 유전자는 GHR 의 발현을 받아 골격근의 성장과 지방 침착을 조절하는 것으 로 밝힌 바 있다 (Lin et al, 2012).…”