Abnormal postnatal maintenance of elevated DLK1 transcript levels in callipyge sheep

Area of Science:

• Genetics
• Animal Science
• Molecular Biology

Background:

• The genetic basis for the callipyge muscular hypertrophy phenotype in sheep (Ovis aries) remains unclear.
• This phenotype, characterized by increased muscle cell size and proportion of glycolytic type II fibers alongside reduced adiposity, manifests postnatally.
• The causative mutation is a single nucleotide change on ovine Chromosome 18, located between the imprinted MATERNALLY EXPRESSED GENE 3 (MEG3) and DELTA, DROSOPHILA, HOMOLOG-LIKE 1 (DLK1) genes, and is only expressed when paternally inherited.

Purpose of the Study:

• To investigate the pre- and postnatal expression patterns of MEG3 and DLK1 in sheep with different genotypes related to the callipyge phenotype.
• To determine the correlation between gene expression anomalies and the manifestation of muscular hypertrophy and altered adiposity.

Main Methods:

• Analysis of MEG3 and DLK1 gene expression in affected and unaffected muscles, as well as liver tissue.
• Comparison of gene expression across all four possible genotypes in sheep exhibiting the callipyge phenotype and controls.
• Examination of gene expression during both pre- and postnatal developmental stages.

Main Results:

• The callipyge phenotype is associated with significantly elevated DLK1 expression in the postnatal period in affected sheep.
• This heightened DLK1 expression is specifically observed in hypertrophy-responsive fast-twitch muscles.
• No significant anomalies were noted in MEG3 expression in relation to the phenotype.

Conclusions:

• The callipyge mutation disrupts the normal postnatal downregulation of DLK1 expression.
• The abnormal DLK1 expression correlates temporally and spatially with the callipyge muscular hypertrophy phenotype.
• This finding provides the first evidence of anomalous gene expression underlying the callipyge phenotype in sheep.