Quantitative analysis of birth, weaning, and yearling weights and calving difficulty in Piedmontese crossbreds segregating an inactive myostatin allele.
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The Piedmontese breed has a high frequency of double-muscling. Animals tested in this breed are homozygous for a guanine to adenine transition in exon 3 (C313Y) of the myostatin (MSTN) gene. This transition seems to be responsible for the double-muscling phenotype. The objective of this study was to compare effects of alternative MSTN genotypes on proportion of assisted calving and weights at birth, weaning, and 1 yr of age. Reciprocal backcross and F2 calves out of Piedmontese-Angus (PA) and Piedmontese-Hereford (PH) dams born in 1995 (n = 82), 1996 (n = 75), and 1997 (n = 144) were evaluated for birth (BWT, kg), adjusted weaning (W200, kg), and yearling (W365, kg) weights and calving difficulty expressed as a proportion of assisted calving (CD). The number of copies of C313Y was assessed in each calf. Data were analyzed with a model that included effects of year, sex, subclasses of proportion Piedmontese (.25, .5, .75) by number of C313Y copies (0 = +/+, 1 = mh/+, 2 = mh/mh), and age of dam as covariate. For BWT, heterozygous mh/+ animals were 3.2 +/- .8 kg heavier than +/+ animals. Homozygous mh/mh animals increased .19 +/- .06 in proportion of CD compared with mh/+ animals. Differences between homozygous animals (mh/mh - +/+) were 5.2 +/- 1 kg for BWT and .21 +/- .06 for CD. Heterozygous mh/+ animals were 9.1 +/- 4 kg heavier at W200 than homozygous +/+ animals. Homozygous +/+ and heterozygous animals were 20 +/- 8 and 24.5 +/- 8 kg, respectively, heavier at W365 than mh/mh animals. Differences between mh/+ and the mean of mh/mh and +/+ genotypes for W200 and W365 were 8.8 +/- 3 and 18 +/- 5 kg, respectively, suggesting dominance effects on postnatal growth. Production of heterozygous animals, to take advantage of the positive impact of one copy of C313Y on carcass traits, may be a viable option when the value of increased retail product yield is greater than the increased cost associated with calving difficulty. (+info)
Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading.
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Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P < 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle. (+info)
Sequence and expression of myoglianin, a novel Drosophila gene of the TGF-beta superfamily.
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Various members of the TGF-beta superfamily of signaling molecules are known to have important roles in mesoderm patterning and differentiation during vertebrate and invertebrate embryogenesis. Here we characterize a new TGF-beta member from Drosophila, Myoglianin, that is most closely related to the vertebrate muscle differentiation factor Myostatin and to vertebrate BMP-11. Northern analysis shows that myoglianin is expressed throughout the Drosophila life cycle. In situ hybridization detects maternally-derived transcripts that are enriched in the pole plasm and later become enclosed in the pole cells. Between stages 11 and 14, myoglianin mRNA is exclusively detected in glial cells and their precursors. Following stage 14, high levels of myoglianin expression are observed in the developing somatic muscles as well as in visceral muscles and cardioblasts. We also show that the zygotic expression of a recently described Drosophila activin, which maps to the same interval 102 on chromosome 4 as myoglianin, is restricted to the developing central and peripheral nervous system. (+info)
Technical note: direct genotyping of the double-muscling locus (mh) in Piedmontese and Belgian Blue cattle by fluorescent PCR.
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A simple PCR-based allele detection system has been developed to assist in the management of the two most prevalent double-muscled (mh) breeds in the U.S. Application of this assay will permit the implementation of structured mating systems dependent on precise genotypes at the mh locus. The genetic assay uses standard fluorescent genotyping technology and relies on the unique nucleotide composition of wild-type and mutant alleles of myostatin, the gene underlying the double-muscled phenotype. We present data demonstrating the efficacy of this fluorescent primer-based PCR assay in genotyping animal populations carrying normal and(or) mutant alleles of the myostatin gene. (+info)
Modulation of myostatin expression during modified muscle use.
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Previous findings have provided strong evidence that myostatin functions as a negative regulator of muscle mass during development and growth. In the present study, we test the hypothesis that myostatin may serve a similar function in fully differentiated muscle experiencing modified loading. Our findings show that myostatin expression can be modulated in fully differentiated, nonpathological skeletal muscle in a manner that is inversely related to changes in muscle mass. Atrophy of rat hind limb muscles induced by 10 days of unloading resulted in a 16% decrease in plantaris mass, a 110% increase in myostatin mRNA, and a 37% increase in myostatin protein. Immunohistochemical observations showed a detectable increase in myostatin concentration at myotendinous junctions during muscle unloading. The concentration of myostatin mRNA and protein returned to values not significantly different from ambulatory controls after 4 days of reloading, during which time plantaris mass also returned to control values. However, the results also show that periods of 30 min of daily muscle loading during the unloading period were sufficient to prevent significant losses of muscle mass caused by unloading, although myostatin mRNA still showed a 55% increase in concentration. Thus, significant increases in myostatin expression are not sufficient for muscle mass loss, although muscle mass loss during unloading is accompanied by increases in myostatin. (+info)
Quantitative trait loci affecting growth and carcass composition of cattle segregating alternate forms of myostatin.
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The effects of the bovine myostatin gene on chromosome 2 on birth and carcass traits have been previously assessed. The objective of this study was to identify additional quantitative trait loci (QTL) for economically important traits in two families segregating an inactive copy of myostatin. Two half-sib families were developed from Belgian Blue x MARC III (n = 246) and Piedmontese x Angus (n = 209) sires. Traits analyzed were birth (kg) and yearling weight (kg); hot carcass weight (kg); fat depth (cm); marbling score; longissimus muscle area (cm2); estimated kidney, pelvic, and heart fat (%); USDA yield grade; retail product yield (%); fat yield (%); and wholesale rib-fat yield (%). Meat tenderness was measured as Warner-Bratzler shear force at 3 and 14 d postmortem. The effect of myostatin on these traits was removed by using phase information obtained from the previous study with six microsatellite markers flanking the locus. Selective genotyping was done on 92 animals from both families to identify genomic regions potentially associated with retail product yield and fat depth, using a total of 150 informative markers in each family. Regions in which selective genotyping indicated the presence of QTL were evaluated further by genotyping the entire population and additional markers. For the family with Belgian Blue inheritance (n = 246), a significant QTL for birth and yearling weight was identified on chromosome 6. Suggestive QTL were identified for longissimus muscle area and hot carcass weight on chromosome 6 and for marbling on chromosomes 17 and 27. For the family with Piedmontese inheritance (n = 209), suggestive QTL on chromosome 5 were identified for fat depth, retail product yield, and USDA yield grade and on chromosome 29 for Warner-Bratzler shear force at 3 and 14 d postmortem. Interactions suggesting the presence of QTL were observed between myostatin and chromosome 5 for Warner-Bratzler shear force at 14 d postmortem and between myostatin and chromosome 14 for fat depth. Thus, in families segregating an inactive copy of myostatin in cattle, other loci influencing quantitative traits can be detected. These results are the initial effort to identify and characterize QTL affecting carcass and growth traits in families segregating myostatin. (+info)
Dominant negative myostatin produces hypertrophy without hyperplasia in muscle.
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Myostatin, a TGF-beta family member, is a negative regulator of muscle growth. Here, we generated transgenic mice that expressed myostatin mutated at its cleavage site under the control of a muscle specific promoter creating a dominant negative myostatin. These mice exhibited a significant (20-35%) increase in muscle mass that resulted from myofiber hypertrophy and not from myofiber hyperplasia. We also evaluated the role of myostatin in muscle degenerative states, such as muscular dystrophy, and found significant downregulation of myostatin. Thus, further inhibition of myostatin may permit increased muscle growth in muscle degenerative disorders. (+info)
Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles.
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Mice genetically deficient in growth and differentiation factor 8 (GDF8/myostatin) had markedly increased muscle fiber numbers and fiber hypertrophy. In the regenerating muscle of mice possessing FGF6 mutation, fiber remodeling was delayed. Although myostatin and FGF6 may be important for the maintenance, regeneration and/or hypertrophy of muscle, little work has been done on the possible role of these proteins in adult muscle in vivo. Using Western blot and immunohistochemical analysis, we investigated, in rats, the distribution of myostatin, FGF6 and LIF proteins between slow- and fast-type muscles, and the adaptive response of these proteins in mechanically overloaded muscles, in regenerating muscles following bupivacaine injection and in denervated muscles after section of the sciatic nerve. The amounts of myostatin and LIF protein were markedly greater in normal slow-type muscles. In the soleus muscle, myostatin and LIF proteins were detected at the site of the myonucleus in both slow-twitch and fast-twitch fibers. In contrast, FGF6 protein was selectively expressed in normal fast-type muscles. Mechanical overloading rapidly enhanced the myostatin and LIF but not FGF6 protein level. In the regenerating muscles, marked diminution of myostatin and FGF6 was observed besides enhancement of LIF. Denervation of fast-type muscles rapidly increased the LIF, but decreased the FGF6 expression. Therefore, the increased expressions of myostatin and LIF play an important role in muscle hypertrophy following mechanical overloading. The marked reduction of FGF6 in the hypertrophied and regenerating muscle would imply that FGF6 regulates muscle differentiation but not proliferation of satellite cells and/or myoblasts. (+info)