Analysis of the callipyge phenotype through skeletal muscle development; association of Dlk1 with muscle precursor cells

Jason D. White, Tony Vuocolo, Matthew McDonagh, Miranda D. Grounds, Gregory S. Harper, Noelle E. Cockett, Ross Tellam

    Research output: Contribution to journalArticle

    44 Citations (Scopus)

    Abstract

    The callipyge mutation in sheep in the form of the paternal heterozygote results in skeletal muscle hypertrophy, which is most pronounced in the hindquarters. Overexpression of one of the genes in the region of the causative single-nucleotide polymorphism, Dlk1, is postulated to be a primary cause of the muscle hypertrophy although the mechanism is not clear. This study examined the expression of Dlk1 mRNA and its encoded protein in skeletal muscles of callipyge and wild-type sheep. The muscles examined included those that demonstrate hypertrophy in callipyge sheep as well as an unaffected muscle. The expression pattern of Dlk1 protein in these muscles was also measured over a developmental time course ranging from 80 days of gestation to 12 weeks after birth. Quantitative reverse transcription-polymerase chain reaction demonstrated that Dlk1 mRNA was significantly increased in affected, but not unaffected, muscles from callipyge sheep at 120 days of gestation through to 12 weeks of age. Immuno-localization of Dlk1 was pronounced in the interstitial connective tissue of fetal muscle but was less intense at later ages. No clear difference in Dlk1 immuno-localization was noted between genotypes in the fetal samples. Strong myofiber-specific Dlk1 immuno-localization was observed in hypertrophied callipyge muscles at 12 weeks of age. This staining was exclusively associated with fast type II myofibers and these had a significantly larger mean cross-sectional area, compared with fast type II myofibers in control sheep that did not overexpress Dlk1. In addition, Dlk1 immuno-localization was associated with a sub-population of Pax7-positive mononucleated cells in all skeletal muscles examined during fetal development and at birth, but this was not apparent at 12 weeks. There were no genotype-dependent alterations in the mRNA expression patterns of a number of promyogenic transcription factors indicating that the callipyge mutation was not affecting muscle cell differentiation per se. We postulate that Dlk1 is implicated in the commitment and/or proliferation of fetal myoblasts as well as in the maintenance of hypertrophy in fully differentiated myofibers.
    Original languageEnglish
    Pages (from-to)283-298
    Number of pages16
    JournalDifferentiation
    Volume76
    Issue number3
    DOIs
    Publication statusPublished - 01 Mar 2008

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