Background: The callipyge mutation is located within an imprinted gene cluster on ovine chromosome 18. The callipyge trait exhibits polar overdominant inheritance due to the fact that only heterozygotes inheriting a mutant paternal allele (paternal heterozygotes) have a phenotype of muscle hypertrophy, reduced fat and a more compact skeleton. The mutation is a single A to G transition in an intergenic region that results in the increased expression of several genes within the imprinted cluster without changing their parent-of-origin allele-specific expression.

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.