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Ectopic Expression of Retrotransposon-Derived PEG11/RTL1 Contributes to the Callipyge Muscular Hypertrophy.

Xu X, Ectors F, Davis EE, Pirottin D, Cheng H, Farnir F, Hadfield T, Cockett N, Charlier C, Georges M, Takeda H - PLoS ONE (2015)

Bottom Line: The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle.We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype.Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep.

View Article: PubMed Central - PubMed

Affiliation: Unit of Animal Genomics, GIGA Research Center and Faculty of Veterinary Medicine, University of Liège, 1 Avenue de l'Hôpital, Liège, Belgium.

ABSTRACT
The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep.

No MeSH data available.


Related in: MedlinePlus

Comparison of PEG11 expression levels in sheep (at 8 weeks of age) and transgenic mice (at 10 weeks of age).Northern blotting performed with 20 μg of total RNA extracted from longissimus dorsi muscles of sheep of the four possible CLPG genotypes (+/+, CLPGMat/+Pat, +Mat/CLPGPat and CLPG/CLPG), or quadriceps femoris muscles of +/+, +/TP, and TP/TP mice from oPEG11 line 126 and probed with a strand-specific RNA probe corresponding first to ovine PEG11, and secondly to mouse β–actin. The bands corresponding presumably to the endogenous ovine PEG11 (sheep PEG11), transgene-derived ovine PEG11 (oPEG11), or β–actin (ACTB/Actb) are marked. Relative quantities were estimated by densitometric analysis of the autoradiograms (a bar graph on the right) suggesting that expression levels of ovine PEG11 are ∼10-fold lower in TP/TP mice from oPEG11 line 126 than in callipyge +Mat/CLPGPat sheep.
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pone.0140594.g005: Comparison of PEG11 expression levels in sheep (at 8 weeks of age) and transgenic mice (at 10 weeks of age).Northern blotting performed with 20 μg of total RNA extracted from longissimus dorsi muscles of sheep of the four possible CLPG genotypes (+/+, CLPGMat/+Pat, +Mat/CLPGPat and CLPG/CLPG), or quadriceps femoris muscles of +/+, +/TP, and TP/TP mice from oPEG11 line 126 and probed with a strand-specific RNA probe corresponding first to ovine PEG11, and secondly to mouse β–actin. The bands corresponding presumably to the endogenous ovine PEG11 (sheep PEG11), transgene-derived ovine PEG11 (oPEG11), or β–actin (ACTB/Actb) are marked. Relative quantities were estimated by densitometric analysis of the autoradiograms (a bar graph on the right) suggesting that expression levels of ovine PEG11 are ∼10-fold lower in TP/TP mice from oPEG11 line 126 than in callipyge +Mat/CLPGPat sheep.

Mentions: Together, our data indicate that postnatal ectopic expression of ovine PEG11 in skeletal muscle of transgenic mice enhances muscle growth, and this strongly supports a contributing role for PEG11 in the muscular hypertrophy of callipyge sheep. The magnitude of the effects observed on muscle weight (less than or equal to 5.3% increase (TP/TPquadriceps)) are modest when compared to those reported in callipyge sheep (f.i. 18.8–21.0% increase in quadriceps [22, 23]). To gain some insights in the possible causes of this discrepancy, we evaluated simultaneously the expression level of ovine PEG11 in +Mat/CLPGPat sheep as well as +/TP and TP/TP transgenic mice by Northern blotting (Fig 5). While the ovine PEG11 transcripts were clearly detectable in skeletal muscle of transgenic mice, their abundance (estimated by densitometry) was ∼10-fold lower than in callipyge sheep (mouse TP/TP versus sheep +mat/Cpat, Fig 5), and this, in addition to the absence of ectopic expression of DLK1, may explain the differences in terms of effect size between mice and sheep.


Ectopic Expression of Retrotransposon-Derived PEG11/RTL1 Contributes to the Callipyge Muscular Hypertrophy.

Xu X, Ectors F, Davis EE, Pirottin D, Cheng H, Farnir F, Hadfield T, Cockett N, Charlier C, Georges M, Takeda H - PLoS ONE (2015)

Comparison of PEG11 expression levels in sheep (at 8 weeks of age) and transgenic mice (at 10 weeks of age).Northern blotting performed with 20 μg of total RNA extracted from longissimus dorsi muscles of sheep of the four possible CLPG genotypes (+/+, CLPGMat/+Pat, +Mat/CLPGPat and CLPG/CLPG), or quadriceps femoris muscles of +/+, +/TP, and TP/TP mice from oPEG11 line 126 and probed with a strand-specific RNA probe corresponding first to ovine PEG11, and secondly to mouse β–actin. The bands corresponding presumably to the endogenous ovine PEG11 (sheep PEG11), transgene-derived ovine PEG11 (oPEG11), or β–actin (ACTB/Actb) are marked. Relative quantities were estimated by densitometric analysis of the autoradiograms (a bar graph on the right) suggesting that expression levels of ovine PEG11 are ∼10-fold lower in TP/TP mice from oPEG11 line 126 than in callipyge +Mat/CLPGPat sheep.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608697&req=5

pone.0140594.g005: Comparison of PEG11 expression levels in sheep (at 8 weeks of age) and transgenic mice (at 10 weeks of age).Northern blotting performed with 20 μg of total RNA extracted from longissimus dorsi muscles of sheep of the four possible CLPG genotypes (+/+, CLPGMat/+Pat, +Mat/CLPGPat and CLPG/CLPG), or quadriceps femoris muscles of +/+, +/TP, and TP/TP mice from oPEG11 line 126 and probed with a strand-specific RNA probe corresponding first to ovine PEG11, and secondly to mouse β–actin. The bands corresponding presumably to the endogenous ovine PEG11 (sheep PEG11), transgene-derived ovine PEG11 (oPEG11), or β–actin (ACTB/Actb) are marked. Relative quantities were estimated by densitometric analysis of the autoradiograms (a bar graph on the right) suggesting that expression levels of ovine PEG11 are ∼10-fold lower in TP/TP mice from oPEG11 line 126 than in callipyge +Mat/CLPGPat sheep.
Mentions: Together, our data indicate that postnatal ectopic expression of ovine PEG11 in skeletal muscle of transgenic mice enhances muscle growth, and this strongly supports a contributing role for PEG11 in the muscular hypertrophy of callipyge sheep. The magnitude of the effects observed on muscle weight (less than or equal to 5.3% increase (TP/TPquadriceps)) are modest when compared to those reported in callipyge sheep (f.i. 18.8–21.0% increase in quadriceps [22, 23]). To gain some insights in the possible causes of this discrepancy, we evaluated simultaneously the expression level of ovine PEG11 in +Mat/CLPGPat sheep as well as +/TP and TP/TP transgenic mice by Northern blotting (Fig 5). While the ovine PEG11 transcripts were clearly detectable in skeletal muscle of transgenic mice, their abundance (estimated by densitometry) was ∼10-fold lower than in callipyge sheep (mouse TP/TP versus sheep +mat/Cpat, Fig 5), and this, in addition to the absence of ectopic expression of DLK1, may explain the differences in terms of effect size between mice and sheep.

Bottom Line: The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle.We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype.Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep.

View Article: PubMed Central - PubMed

Affiliation: Unit of Animal Genomics, GIGA Research Center and Faculty of Veterinary Medicine, University of Liège, 1 Avenue de l'Hôpital, Liège, Belgium.

ABSTRACT
The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep.

No MeSH data available.


Related in: MedlinePlus