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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

Phenotypic effects of one (+/TP) and two (TP/TP) copies of the oPEG11 transgene (line 126) in the oPEG11 F1 mouse cross (+/TP x +/TP) at 10 weeks of age.The eight graphs show the distribution of individual phenotypic values corrected for sex and litter effects (carcass weight, the weight of the hind legs, quadriceps and lung and their ratios to live weight (LW)) of mice sorted by transgene genotype. Ratios were subject to angular transformation. Genotype means are shown by black dots with error bars (± 1.96 s.e.m.). Statistically significant differences between the possible combinations of genotype computed with the mixed model and Tukey honest significant difference test are marked by braces; ***: p < 0.001, **: p < 0.01, *: p < 0.05 (S2 Table); n = 68 (+/+), 122 (+/TP) and 55 (TP/TP).
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pone.0140594.g003: Phenotypic effects of one (+/TP) and two (TP/TP) copies of the oPEG11 transgene (line 126) in the oPEG11 F1 mouse cross (+/TP x +/TP) at 10 weeks of age.The eight graphs show the distribution of individual phenotypic values corrected for sex and litter effects (carcass weight, the weight of the hind legs, quadriceps and lung and their ratios to live weight (LW)) of mice sorted by transgene genotype. Ratios were subject to angular transformation. Genotype means are shown by black dots with error bars (± 1.96 s.e.m.). Statistically significant differences between the possible combinations of genotype computed with the mixed model and Tukey honest significant difference test are marked by braces; ***: p < 0.001, **: p < 0.01, *: p < 0.05 (S2 Table); n = 68 (+/+), 122 (+/TP) and 55 (TP/TP).

Mentions: Sixteen F1 pairs carrying the oPEG11 line 126 transgene in a pure FVB background were intercrossed to generate 245 F2 offspring from 28 litters. The average number of offspring per litter was 9, ranging from 4 to 12, hence within the normal range for FVB mice. Sex ratios and genotype frequencies (+/+, +/T(ransgene)P and TP/TP) did not deviate significantly from expectations (S1 Table). All animals were weighted weekly after weaning, euthanized at ~10 weeks of age (range: 70–74 days) and dissected. For each animal, we recorded live weight, carcass weight, the weight of the hind legs, quadriceps femoris muscles, triceps brachialis muscles, kidney, spleen, liver and heart. The weight of the hind leg is primarily determined by the mass of the muscle (85.6 ± 1.9%, n = 3). Phenotypic values were analyzed with a mixed model including sex and genotype as fixed effects, and litter as random effect (Model-1, S2 Table). Sex-by-genotype interactions were considered but never significant and therefore not included in the model. Transgene genotype significantly affected the weight of the carcass (p = 1.5x10-4), hind legs (p = 2.0x10-7), quadriceps (p = 2.8x10-6), and triceps (p = 2.5x10-3) (Fig 3; S2 Table). More specifically, one and two copies of the transgene increased carcass weight by 2.3% (p = 6.4x10-3) and 3.7% (p = 7.4x10-5), and the weight of the hind legs by 3.0% (p = 2.6x10-4) and 5.2% (p = 3.4x10-8), respectively. For individual muscles the corresponding increases were 3.0% (p = 1.4x10-3) and 5.3% (p = 1.4x10-6) for quadriceps, and 1.7% (not significant) and 3.7% (p = 1.3x10-3) for triceps.


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)

Phenotypic effects of one (+/TP) and two (TP/TP) copies of the oPEG11 transgene (line 126) in the oPEG11 F1 mouse cross (+/TP x +/TP) at 10 weeks of age.The eight graphs show the distribution of individual phenotypic values corrected for sex and litter effects (carcass weight, the weight of the hind legs, quadriceps and lung and their ratios to live weight (LW)) of mice sorted by transgene genotype. Ratios were subject to angular transformation. Genotype means are shown by black dots with error bars (± 1.96 s.e.m.). Statistically significant differences between the possible combinations of genotype computed with the mixed model and Tukey honest significant difference test are marked by braces; ***: p < 0.001, **: p < 0.01, *: p < 0.05 (S2 Table); n = 68 (+/+), 122 (+/TP) and 55 (TP/TP).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140594.g003: Phenotypic effects of one (+/TP) and two (TP/TP) copies of the oPEG11 transgene (line 126) in the oPEG11 F1 mouse cross (+/TP x +/TP) at 10 weeks of age.The eight graphs show the distribution of individual phenotypic values corrected for sex and litter effects (carcass weight, the weight of the hind legs, quadriceps and lung and their ratios to live weight (LW)) of mice sorted by transgene genotype. Ratios were subject to angular transformation. Genotype means are shown by black dots with error bars (± 1.96 s.e.m.). Statistically significant differences between the possible combinations of genotype computed with the mixed model and Tukey honest significant difference test are marked by braces; ***: p < 0.001, **: p < 0.01, *: p < 0.05 (S2 Table); n = 68 (+/+), 122 (+/TP) and 55 (TP/TP).
Mentions: Sixteen F1 pairs carrying the oPEG11 line 126 transgene in a pure FVB background were intercrossed to generate 245 F2 offspring from 28 litters. The average number of offspring per litter was 9, ranging from 4 to 12, hence within the normal range for FVB mice. Sex ratios and genotype frequencies (+/+, +/T(ransgene)P and TP/TP) did not deviate significantly from expectations (S1 Table). All animals were weighted weekly after weaning, euthanized at ~10 weeks of age (range: 70–74 days) and dissected. For each animal, we recorded live weight, carcass weight, the weight of the hind legs, quadriceps femoris muscles, triceps brachialis muscles, kidney, spleen, liver and heart. The weight of the hind leg is primarily determined by the mass of the muscle (85.6 ± 1.9%, n = 3). Phenotypic values were analyzed with a mixed model including sex and genotype as fixed effects, and litter as random effect (Model-1, S2 Table). Sex-by-genotype interactions were considered but never significant and therefore not included in the model. Transgene genotype significantly affected the weight of the carcass (p = 1.5x10-4), hind legs (p = 2.0x10-7), quadriceps (p = 2.8x10-6), and triceps (p = 2.5x10-3) (Fig 3; S2 Table). More specifically, one and two copies of the transgene increased carcass weight by 2.3% (p = 6.4x10-3) and 3.7% (p = 7.4x10-5), and the weight of the hind legs by 3.0% (p = 2.6x10-4) and 5.2% (p = 3.4x10-8), respectively. For individual muscles the corresponding increases were 3.0% (p = 1.4x10-3) and 5.3% (p = 1.4x10-6) for quadriceps, and 1.7% (not significant) and 3.7% (p = 1.3x10-3) for triceps.

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