Grobet, L., Royo Martin, J. L., Poncelet, D., Pirottin, D., Brouwers, B., Riquet, J et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature Genet, 17: 71-74
An exceptional muscle development commonly referred to as 'double-muscled' (Fig. 1) has been seen in several cattle breeds and has attracted considerable attention from beef producers. Double-muscled animals are characterized by an increase in muscle mass of about 20%, due to general skeletal-muscle hyperplasia-that is, an increase in the number of muscle fibers rather than in their individual diameter. Although the hereditary nature of the double-muscled condition was recognized early on, the precise mode of inheritance has remained controversial; monogenic (domainant and recessive), oligogenic and polygenic models have been proposed. In the Belgian Blue cattle breed (BBCB), segregation analysis performed both in experimental crosses and in the outbred population suggested an autosomal recessive inheritance. This was confirmed when the muscular hypertrophy (mh) locus was mapped 3.1 cM from microsatellite TGLA44 on the centromeric end of bovine chromosome 2 (ref. 5). We used a positional candidate approach to demonstrate that a mutation in bovine MSTN, which encodes myostatin, a member of the TGF beta superfamily, is responsible for the double-muscled phenotype. We report an 11-bp deletion in the coding sequence for the bioactive carboxy-terminal domain of the protein causing the muscular hypertrophy observed in Belgian Blue cattle.
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"Moreover, marbling is determined polygenically. Genetics plays a key role in mediating the composition of bovine muscle tissues (Grobet et al., 1997). However, the complexity of the bovine transcriptome has not yet been fully elucidated. "
[Show abstract][Hide abstract] ABSTRACT: Marbling is an important trait regarding the quality of beef. Analysis of beef cattle transcriptome and its expression profile data are essential to extend the genetic information resources and would support further studies on beef cattle. RNA sequencing was performed in beef cattle using the Illumina High-Seq2000 platform. Approximately 251.58 million clean reads were generated from a high marbling (H) group and low marbling (L) group. Approximately 80.12% of the 19,994 bovine genes (protein coding) were detected in all samples, and 749 genes exhibited differential expression between the H and L groups based on fold change (>1.5-fold, p<0.05). Multiple gene ontology terms and biological pathways were found significantly enriched among the differentially expressed genes. The transcriptome data will facilitate future functional studies on marbling formation in beef cattle and may be applied to improve breeding programs for cattle and closely related mammals.
Full-text · Article · Feb 2015 · Asian Australasian Journal of Animal Sciences
"It is well known that skeletal muscle development is negatively regulated by myostatin (MSTN) gene, which is a member of the transforming growth factor-β (TGF-β) family and is predominantly expressed and secreted by skeletal muscle cells. Mutations in the myostatin gene cause a hypertrophic phenotype have been widely reported in many species, including sheep 2, 3, cattle 4, 5, dog 6, mice 7, and human 8. Moreover, many evidences have showed that GDF8 mutant has redder muscle fibers with more intramuscular fat and faster growth than those of the indigenous sheep 3, 9. Texel sheep, a typical breed with "double muscle" due to a GDF8 mutation, are more muscular than those indigenous such as Ujumqin sheep 10. "
[Show abstract][Hide abstract] ABSTRACT: Background: Muscle development and lipid metabolism play important roles during fetal development stages. The commercial Texel sheep are more muscular than the indigenous Ujumqin sheep.
Results: We performed serial transcriptomics assays and systems biology analyses to investigate the dynamics of gene expression changes associated with fetal longissimus muscles during different fetal stages in two sheep breeds. Totally, we identified 1472 differentially expressed genes during various fetal stages using time-series expression analysis. A systems biology approach, weighted gene co-expression network analysis (WGCNA), was used to detect modules of correlated genes among these 1472 genes. Dramatically different gene modules were identified in four merged datasets, corresponding to the mid fetal stage in Texel and Ujumqin sheep, the late fetal stage in Texel and Ujumqin sheep, respectively. We further detected gene modules significantly correlated with fetal weight, and constructed networks and pathways using genes with high significances. In these gene modules, we identified genes like TADA3, LMNB1, TGF-β3, EEF1A2, FGFR1, MYOZ1, and FBP2 correlated with fetal weight.
Conclusion: Our study revealed the complex network characteristics involved in muscle development and lipid metabolism during fetal development stages. Diverse patterns of the network connections observed between breeds and fetal stages could involve some hub genes, which play central roles in fetal development, correlating with fetal weight. Our findings could provide potential valuable biomarkers for selection of body weight-related traits in sheep and other livestock.
Full-text · Article · Sep 2014 · International journal of biological sciences
"Myostatin is a member of the transforming growth factor (TGF)-β family which negatively regulates myogenesis at multiple levels [58,59]. Myostatin inhibits muscle growth and development via Smad dependent and independent pathways resulting in decreased protein synthesis and satellite cell proliferation [60,61]. "
[Show abstract][Hide abstract] ABSTRACT: Background
Maternal over and restricted nutrition has negative consequences on the muscle of offspring by reducing muscle fiber number and altering regulators of muscle growth. To determine if over and restricted maternal nutrition affected muscle growth and gene and protein expression in offspring, 36 pregnant ewes were fed 60%, 100% or 140% of National Research Council requirements from d 31 ± 1.3 of gestation until parturition. Lambs from control-fed (CON), restricted-fed (RES) or over-fed (OVER) ewes were necropsied within 1 d of birth (n = 18) or maintained on a control diet for 3 mo (n = 15). Semitendinosus muscle was collected for immunohistochemistry, and protein and gene expression analysis.
Compared with CON, muscle fiber cross-sectional area (CSA) increased in RES (58%) and OVER (47%) lambs at 1 d of age (P < 0.01); however at 3 mo, CSA decreased 15% and 17% compared with CON, respectively (P < 0.01). Compared with CON, muscle lipid content was increased in OVER (212.4%) and RES (92.5%) at d 1 (P < 0.0001). Muscle lipid content was increased 36.1% in OVER and decreased 23.6% in RES compared with CON at 3 mo (P < 0.0001). At d 1, myostatin mRNA abundance in whole muscle tended to be greater in OVER (P = 0.07) than CON. Follistatin mRNA abundance increased in OVER (P = 0.04) and tended to increase in RES (P = 0.06) compared with CON at d 1. However, there was no difference in myostatin or follistatin protein expression (P > 0.3). Phosphorylated Akt (ser473) was increased in RES at 3 mo compared with CON (P = 0.006).
In conclusion, maternal over and restricted nutrient intake alters muscle lipid content and growth of offspring, possibly through altered gene and protein expression.
Full-text · Article · Sep 2014 · Journal of Animal Science and Biotechnology