Postnatal changes in the expression of genes located in the callipyge region in sheep skeletal muscle.
ABSTRACT The expression of five genes surrounding the callipyge (CLPG) mutation was analysed in skeletal muscles from lambs at one prenatal and two postnatal ages that coincide with the onset and establishment of muscle hypertrophy. Genotype-specific changes in transcript abundance were detected for paternal allele-specific DLK1 and PEG11 (the official symbol of the latter is RTL1) and the maternal allele-specific MEG3, PEG11AS and MEG8 when the mutation was inherited in cis. There were differences in the temporal and muscle-specific effects on expression between the maternal allele-specific genes and paternal allele-specific genes. Maternal inheritance of the CLPG allele had a significant effect on the expression of MEG3 and MEG8 at prenatal and postnatal ages, whereas paternal inheritance of DLK1 and PEG11 only affected postnatal expression. Genotype-specific changes in PEG11AS expression were detected only in prenatal muscle. Maternal inheritance of the mutation caused similar changes in MEG3 and MEG8 expression in the semimembranosus, which undergoes hypertrophy, and the supraspinatus, which does not hypertrophy. Paternal inheritance of the mutation caused changes in PEG11 expression in both muscles, although the magnitude of expression in semimembranosus was more than 100-fold greater than in supraspinatus. DLK1 expression was upregulated in callipyge animals at both postnatal ages in the semimembranosus, but there was no effect of genotype on DLK1 expression in the supraspinatus at any age. Increased DLK1 expression was likely the primary cause of muscle hypertrophy, but a contribution of PEG11 to the phenotype cannot be ruled out based on gene expression.
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ABSTRACT: Two ovine BAC clones and a connecting long-range PCR product, jointly spanning approximately 250 kb and representing most of the MULGE5-OY3 marker interval known to contain the clpg locus, were completely sequenced. The resulting genomic sequence was aligned with its human ortholog and extensively annotated. Six transcripts, four of which were novel, were predicted to originate from within the analyzed region and their existence confirmed experimentally: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8. RT-PCR experiments performed on a range of tissues sampled from an 8-wk-old animal demonstrated the preferential expression of all six transcripts in skeletal muscle, which suggests that they are under control of common regulatory elements. The six transcripts were also shown to be subject to parental imprinting: DLK1, DAT, and PEG11 were shown to be paternally expressed and GTL2, antiPEG11, and MEG8 to be maternally expressed.Genome Research 06/2001; 11(5):850-62. · 14.40 Impact Factor
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ABSTRACT: The histology and composition of muscles from normal (n = 10) and callipyge (n = 11) wether lambs was compared. Normal Rambouillet ewes were mated with callipyge Dorset rams, and their progeny were visually classified as callipyge or normal based on muscle definition in the loin and hind quarters. The muscles examined included three muscles that hypertrophy in callipyge lambs (semitendinosus, longissimus, and gluteus medius) and one muscle believed not to hypertrophy (supraspinatus). The hypertrophy-responsive muscles from callipyge lambs had a higher (P < .001) percentage of fast-twitch glycolytic (FG) fibers and lower (P < .001; P < .02 for SO in gluteus medius) percentages of slow-twitch oxidative (SO) and fast-twitch oxidative glycolytic (FOG) fibers. The diameters of the FG and FOG fibers were larger (P < .005 and P < .04, respectively) in hypertrophy-responsive muscles from callipyge lambs, but the SO fiber diameter was smaller (P < .05). Also, the protein:DNA ratio, an indicator of cell size, was greater (semitendinosus, P < .05); longissimus, P < .002; gluteus medius, P < .008) in the hypertrophy-responsive muscles from callipyge lambs. Thus, hypertrophy in callipyge lambs was, at least in part, due to fiber type changes and muscle cell enlargement. Hypertrophy was strongly associated with changes in the FG fibers, the only fiber type that increased in both proportion and average diameter in callipyge muscles. The protein:RNA ratio and RNA:DNA ratio, which are indicators of translational and transcriptional activity in the muscle cells, were not different between callipyge and normal muscles. This indicated that the accumulation of protein necessary for myofiber enlargement occurred without differences in the translational or transcriptional activity of callipyge muscle.Journal of Animal Science 03/1996; 74(2):388-93. · 2.09 Impact Factor
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ABSTRACT: The callipyge phenotype in sheep is an inherited muscular hypertrophy that affects only heterozygous individuals who receive the CLPG mutation from their father. The CLPG mutation is a single nucleotide substitution in what is probably a long-range control element (LRCE) within the DLK1-GTL2 imprinted domain. Recent results suggest that the unique mode of inheritance of callipyge, referred to as polar overdominance, results from the combination of the cis-effect of the CLPG mutation on the expression levels of genes in the DLK1-GTL2 imprinted domain, and the trans interaction between the products of reciprocally imprinted genes.Trends in Genetics 06/2003; 19(5):248-52. · 9.77 Impact Factor