Analysis of gene expression during the onset of muscle hypertrophy in callipyge lambs

Fleming-Waddell, Jolena N.; Wilson, Leah M.; Olbricht, Gayla R.; Vuocolo, Tony; Byrne, Keren; Craig, Bruce A.; Tellam, Ross L.; Cockett, Noelle E.; Bidwell, Christopher A.

doi:10.1111/j.1365-2052.2006.01562.x

Cited by 46 publications

(51 citation statements)

References 43 publications

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“…Multiple lines of evidence suggest that the over growth of muscle mass observed in the CLPG phenotype may result from elevated expression of the DLK1 protein (4,8,30). We therefore measured Dlk1 mRNA levels in the GAST muscles of the mutant mice.…”

Section: Significancementioning

confidence: 99%

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Gao

Chen

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Inheritance of the callipyge phenotype in sheep is an example of polar overdominance inheritance, an unusual mode of inheritance. To investigate the underlying molecular mechanism, we profiled the expression of the genes located in the Delta-like 1 homolog (Dlk1)-type III iodothyronine deiodinase (Dio3) imprinting region in mice. We found that the transcripts of the microRNA (miR) 379/miR-544 cluster were highly expressed in neonatal muscle and paralleled the expression of the Dlk1. We then determined the in vivo role of the miR-379/miR-544 cluster by establishing a mouse line in which the cluster was ablated. The maternal heterozygotes of young mutant mice displayed a hypertrophic tibialis anterior muscle, extensor digitorum longus muscle, gastrocnemius muscle, and gluteus maximus muscle and elevated expression of the DLK1 protein. Reduced expression of DLK1 was mediated by miR-329, a member of this cluster. Our results suggest that maternal expression of the imprinted miR-379/miR-544 cluster regulates paternal expression of the Dlk1 gene in mice. We therefore propose a miR-based molecular working model for polar overdominance inheritance. muscle hypertrophy | callipyge | DLK1 | miR-379/miR-544 cluster T he callipyge (CLPG) phenotype can be characterized by an increase in muscle mass due to muscular hypertrophy and a unique non-Mendelian mode of inheritance (1-3). CLPG individuals are born with normal muscle histology and develop muscle hypertrophy at ∼1 mo of age. This hypertrophy occurs primarily in the muscles of the pelvic limbs and loin and some muscles in the shoulder, which are enriched with a high proportion of type IIB fast-twitch glycolytic fibers (4). Although the molecular regulation of these hypertrophic processes is yet to be determined, Delta-like 1 homolog (DLK1) is found to be the causative protein (5-10). The unique mode of inheritance of the CLPG phenotype has attracted a great deal of attention within the scientific community. The CLPG offspring inherit the phenotype only when the mutated allele comes from the father and the wild-type allele from the mother (CLPG PAT /+ MAT ). CLPG PAT /CLPG MAT offspring exhibit a wild-type phenotype, despite carrying a CLPG mutation on the paternal chromosome. This unusual mode of inheritance led to the development of the genetic concept of polar overdominance (2, 11).The CLPG mutation has been mapped to the Dlk1-Dio3 imprinted domain, which spans ∼1 Mb and harbors at least three protein-encoding genes, including Dlk1, Peg11/Rtl1, and Dio3, and multiple noncoding RNA genes, including Gtl2, anti-Peg11/anti-Rtl1, Meg8, Mirg, C/D small nucleolar RNAs (snoRNAs), and microRNA clusters [the microRNA (miR) 379 and miR-127 clusters] (12-14). The coding genes are expressed paternally, whereas the noncoding genes are expressed maternally (15,16). Further analysis revealed a point mutation (A to G transition) within the intergenic region between the Dlk1 and Gtl2 genes of the imprinted Dlk1-Dio3 region (17, 18), which affects a muscle-specific, long-range cis-acting ...

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Section: Significancementioning

confidence: 99%

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Gao

Chen

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…qRT-PCR was performed and the amount of amplified DNA was monitored by fluorescence at the end of each cycle using CFX 96 (Bio-Rad Laboratories). Thermal cycling consisted of an initial step at 95°C for 110 s followed by 40 cycles at 95°C for 10 s and 61°C for 33 s. RPLP0 was chosen as the reference gene for normalization of all data because it was expressed more stably (Laborda, 1991;Fleming-Waddell et al, 2007;Vuocolo et al, 2007;White et al, 2008). Each qRT-PCR N. Liu et al…”

Section: Quantitative Real-time Pcr (Qrt-pcr) For Microarray Datamentioning

confidence: 99%

Transcriptome analysis of skeletal muscle at prenatal stages in Polled Dorset versus Small-tailed Han sheep

Liu

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The objectives of the present study were to identify additional genes that may play important roles in the regulation of skeletal muscle growth and development, and to provide fundamental information for understanding the underlying molecular mechanisms. Eighteen cDNA libraries were constructed from the longissimus muscle of Polled Dorset (PD) and Small-tailed Han (SH) fetuses. To reveal the differences between the two species, we analyzed the differences in gene expression in 60-, 90-and 120-day fetal skeletal muscle by applying Agilent ovine genome-wide microarray. In this study, we obtained 17,704 genes using a chip containing 39,242 probes. There were 88 differentially expressed genes in the 60-day group (P < 0.05), 128 genes in the 90-day group (P < 0.05), and 340 genes in the 120-day group (P < 0.05) between the two breeds. The differentially expressed genes were grouped in different GO categories and signaling pathways. These results suggested that there are many genetic differences in the muscle growth and development transcriptomes between these two breeds. This study laid the foundation for future genomic research in sheep.

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“…Using the Affymetrix Bovine Expression Array technique, Fleming-Waddell et al (2007) identified a particular gene expression profile in skeletal muscle of sheep carrying the callipyge mutation. Studies of gene expression profiles in sheep muscles by Lobo et al (2012) revealed differential expression of MyoD1 and IGFBP4 genes associated with breed and productive qualities.…”

Section: Introductionmentioning

confidence: 99%

Correlation between gene expression profiles in muscle and live weight in Dzhalginsky Merino sheep

Skripkin

Квочко

Куличенко

et al. 2016

Rev Colomb Cienc Pecu

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Analysis of gene expression during the onset of muscle hypertrophy in callipyge lambs

Cited by 46 publications

References 43 publications

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Transcriptome analysis of skeletal muscle at prenatal stages in Polled Dorset versus Small-tailed Han sheep

Correlation between gene expression profiles in muscle and live weight in Dzhalginsky Merino sheep

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