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PMID:19247431

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Citation

da Rocha, ST, Charalambous, M, Lin, SP, Gutteridge, I, Ito, Y, Gray, D, Dean, W and Ferguson-Smith, AC (2009) Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting. PLoS Genet. 5:e1000392

Abstract

Genomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double, and triple dosage of the imprinted Dlk1/Pref1, normally repressed on the maternally inherited chromosome, can be assessed in the growing embryo. BAC-transgenic mice were generated that over-express Dlk1 from endogenous regulators at all sites of embryonic activity. Triple dosage causes lethality associated with major organ abnormalities. Embryos expressing a double dose of Dlk1, recapitulating loss of imprinting, are growth enhanced but fail to thrive in early life, despite the early growth advantage. Thus, any benefit conferred by increased embryonic size is offset by postnatal lethality. We propose a negative correlation between gene dosage and survival that fixes an upper limit on growth promotion by Dlk1, and we hypothesize that trade-off between growth and lethality might have driven imprinting at this locus.

Links

PubMed PMC2640098 Online version:10.1371/journal.pgen.1000392

Keywords

Animals; Bone and Bones/embryology; Bone and Bones/metabolism; Embryonic Development; Evolution, Molecular; Female; Gene Dosage; Gene Expression Regulation, Developmental; Genomic Imprinting; Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Skeletal/embryology; Muscle, Skeletal/growth & development; Muscle, Skeletal/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DLK1

acts_upstream_of_or_within

GO:0009791: post-embryonic development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DLK1

acts_upstream_of_or_within

GO:0048706: embryonic skeletal system development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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