Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.12.09.627469

Transcriptomic Analysis Reveals MSTN Mutations and Mechanisms of Muscle Hypertrophy in a New Guinea Pig Breed

Abstract

The guinea pig (Cavia porcellus), a species native to Peru, is valued for its meat production, where muscle development is essential for productive efficiency. The new Kuri breed, obtained through selective breeding and genetic selection, has shown a phenotype with more developed musculature compared to native guinea pigs. In this study, we conducted a comparative transcriptomic analysis between Native and Kuri breed guinea pig, complemented by histological analysis of the semitendinosus muscle to investigate the underlying mechanisms responsible for the differences in muscle morphology. Histological analysis revealed a significant increase in muscle fiber area in the Kuri breed compared to the native guinea pigs. At the molecular level, key mutations were identified in the MSTN gene, including variants in the 3 UTR region and a frameshift mutation, which alter the genes inhibitory function on muscle growth. Additionally, differences were observed in the expression of pathways related to muscle degradation, energy metabolism, and angiogenesis, which explain the greater muscle hypertrophy in the Kuri breed. These findings provide a first understanding of the genetic mechanisms responsible for muscle hypertrophy in the Kuri breed and suggest candidate genes for improving meat quality through molecular genetic breeding programs in guinea pigs. AUTHOR SUMMARYThe guinea pig in Peru is valued for its meat production. The new Kuri breed, obtained through selective breeding and genetic selection has shown a phenotype with more developed musculature compared to other breeders. In our study, comparative transcriptomic analysis between Native and Kuri breed guinea pig, complemented by histological analysis of the semitendinosus muscle to investigate the underlying mechanisms responsible for the differences in muscle morphology. Histological analysis showed significant increase in muscle fiber area in the Kuri breed compared to the native. Furthermore, it is the first time that we identify in guinea pig, key mutations in the MSTN gene, which alter the genes inhibitory function on muscle growth. The impact of this finding will allow us to plan genetic improvement strategies in this species that promote muscle hypertrophy, paving the way for future research and its potential impact on guinea pig production.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Carmen, S., Chauca, L., Yalta, C., Alvarado, E., Mellisho, E.. 2024-12-09. Transcriptomic Analysis Reveals MSTN Mutations and Mechanisms of Muscle Hypertrophy in a New Guinea Pig Breed. https://doi.org/10.1101/2024.12.09.627469

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Engineered Miniature ParTasR Enables Efficient PAMless Genome Editing

TIGR-Tas system holds great promise for genome-engineering applications owing to its compact size and PAMless targeting capability. However, its low editing efficiency in mammalian cells severely limits its broader utility. Here, we engineered a highly active variant of ParTasR, termed eTasR, through structure-guided rational design of ParTasR combined with fusion to the exonuclease TREX2. eTasR increased mammalian editing efficiency from the original 4.29% to 48.94% with an average 26.52-fold increase, significantly surpassing the efficiency of SpRY, a reported version of PAM-free nuclease. More importantly, single-AAV delivery enabled efficient Hpd disruption in vivo, resulting in robust phenotypic rescue. Thus, eTasR provides a compact, PAMless and highly efficient platform for genome editing and therapeutic applications.

molecular biology↗

Enhancing pancreatic islet cell survival via NMDAR antagonist-driven ROR1 activation as revealed by phosphoproteomics

NMDA receptors (NMDARs) control function and survival not only of neurons, but also of insulin-producing pancreatic beta cells. Since insufficient insulin secretion and beta cell death are key events during diabetes development, targeting NMDARs offers a therapeutic approach. Specifically, the NMDAR antagonist dextrorphan (DXO) increases glucose-stimulated insulin secretion in clinical trials. Furthermore, treatment with DXO or optimized DXO derivatives prevents pancreatic islet cell death upon diabetogenic insults. Nonetheless, the signaling pathways induced by NMDAR inhibition are poorly understood. Here, we use complementary approaches, phosphoproteomics and tyrosine kinase profiling, to demonstrate that DXO and its derivatives rapidly regulate multiple intracellular signaling clusters, including mTOR and ERK signaling, in pancreatic islets. Notably, mTOR inhibition, but not ERK inhibition, is sufficient to negate DXO's protective effects. Further, we show that activation of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) is a universal event upon NMDAR inhibition in islets. Simultaneous knockdown of Ror1/ROR1 and its paralogue Ror2/ROR2 compromises the viability of both mouse and human islets, highlighting the ROR1/2 signaling axis as a promising avenue for enhancing beta cell survival.

molecular biology↗

An ssRNA Phage Single-gene Lysis Protein Targeting MraY Reveals Convergent Evolution Across the RNA-DNA Phage Boundary

Small lytic phages of the ssRNA Leviviricetes and ssDNA Microviricetes achieve host lysis by expression of a single protein, designated as an Sgl protein. Four ssRNA Sgls have been shown to inhibit steps in peptidoglycan biosynthesis: three target MurJ, the Lipid II flippase, and one targets MurA, the committed step of the pathway. A fifth Sgl, the E protein of the canonical ssDNA microvirus {varphi}X174, inhibits MraY, which catalyzes the synthesis of the first lipid-linked intermediate. This inhibition requires SlyD, a cytoplasmic FKBP-type peptidyl-prolyl cis-trans isomerase. The Sgl of the Caulobacter ssRNA phage {varphi}Cb5 (Cebevirus halophobicum) has not been characterized. Here, we present physiological evidence that Sgl{varphi}Cb5 targets MraY. Moreover, we show that, despite the absence of detectable sequence similarity, Sgl{varphi}Cb5 shares several features with the {varphi}X174 E protein, including the distribution of hydrophobic and charged residues, a proposed N-out, C-in membrane topology, and retention of lytic activity in an Sgl{varphi}Cb5 -LacZ fusion. Furthermore, expression of the Caulobacter cytoplasmic FKBP-type peptidyl-prolyl cis-trans isomerase CC2799 enhances Sgl{varphi}Cb5 -mediated lysis in E. coli. These parallels between Sgl function in a DNA phage and an RNA phage either represent remarkably consonant convergent evolution or some evolutionary cross-over event for which there is currently no precedent.

molecular biology↗