Abnormal postnatal maintenance of elevated DLK1 transcript levels in callipyge sheep.
The underlying mechanism of the callipyge muscular hypertrophy phenotype in sheep (Ovis aries) is not presently understood. This phenotype, characterized by increased glycolytic type II muscle proportion and cell size accompanied by decreased adiposity, is not visibly detectable until approximately three to eight weeks after birth. The muscular hypertrophy results from a single nucleotide change located at the telomeric end of ovine Chromosome 18, in the region between the imprinted MATERNALLY EXPRESSED GENE 3 (MEG3) and DELTA, DROSOPHILA, HOMOLOG-LIKE 1 (DLK1) genes. The callipyge phenotype is evident only when the mutation is paternally inherited by a heterozygous individual. We have examined the pre- and postnatal expression of MEG3 and DLK1 in sheep of all four possible genotypes in affected and unaffected muscles as well as in liver. Here we show that the callipyge phenotype correlates with abnormally high DLK1 expression during the postnatal period in the affected sheep and that this elevation is specific to the hypertrophy-responsive fast-twitch muscles. These results are the first to show anomalous gene expression that coincides with both the temporal and spatial distribution of the callipyge phenotype. They suggest that the effect of the callipyge mutation is to interfere with the normal postnatal downregulation of DLK1 expression.
Murphy
Susan K
SK
Department of Radiation Oncology, Duke University, Box 3433, Durham, North Carolina 27710, USA.
Freking
Brad A
BA
Smith
Timothy P L
TP
Leymaster
Kreg
K
Nolan
Catherine M
CM
Wylie
Andrew A
AA
Evans
Heather K
HK
Jirtle
Randy L
RL
D000818:Animals; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006579:Heterozygote; D006614:Hindlimb / Q000002:abnormalities / Q000254:growth & development; D006984:Hypertrophy; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000378:metabolism / Q000662:veterinary*; D012757:Sheep Diseases / Q000378:metabolism*; D034561:Sheep, Domestic / Q000235:genetics* / Q000254:growth & development
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein