Mice Lacking Paternally Expressed Pref-1/Dlk1 Display Growth Retardation and Accelerated Adiposity
- 1 August 2002
- journal article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 22 (15), 5585-5592
- https://doi.org/10.1128/mcb.22.15.5585-5592.2002
Abstract
Preadipocyte factor 1 (Pref-1/Dlk1) inhibits in vitro adipocyte differentiation and has been recently reported to be a paternally expressed imprinted gene at human chromosome 14q32. Studies on human chromosome 14 deletions and maternal uniparental disomy (mUPD) 14 suggest that misexpression of a yet-to-be-identified imprinted gene or genes present on chromosome 14 causes congenital disorders. We generated Pref-1 knockout mice to assess the role of Pref-1 in growth and in vivo adipogenesis and to determine the contribution of Pref-1 in mUPD. Pref-1-null mice display growth retardation, obesity, blepharophimosis, skeletal malformation, and increased serum lipid metabolites. Furthermore, the phenotypes observed in Pref-1-null mice are present in heterozygotes that harbor a paternally inherited, but not in those with a maternally inherited pref-1-null allele. Our results demonstrate that Pref-1 is indeed paternally expressed and is important for normal development and for homeostasis of adipose tissue mass. We also suggest that Pref-1 is responsible for most of the symptoms observed in mouse mUPD12 and human mUPD14. Pref-1-null mice may be a model for obesity and other pathologies of human mUPD14.Keywords
This publication has 35 references indexed in Scilit:
- Regulatory Mechanisms at the MouseIgf2/H19 LocusMolecular and Cellular Biology, 2001
- Complex and segmental uniparental disomy (UPD): review and lessons from rare chromosomal complementsJournal of Medical Genetics, 2001
- Human–Ovine Comparative Sequencing of a 250-kb Imprinted Domain Encompassing the Callipyge (clpg) Locus and Identification of Six Imprinted Transcripts: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8Genome Research, 2001
- dlk Inhibits Stem Cell Factor‐Induced Colony Formation of Murine Hematopoietic Progenitors: Hes‐1‐Independent EffectThe International Journal of Cell Cloning, 2001
- Transcriptional Repression of pref-1by Glucocorticoids Promotes 3T3-L1 Adipocyte DifferentiationPublished by Elsevier BV ,1999
- Maternal uniparental disomy 7 in Silver-Russell syndrome.Journal of Medical Genetics, 1997
- Molecular Mechanisms of Adipocyte Differentiation and Inhibitory Action of Pref-1Critical Reviews™ in Eukaryotic Gene Expression, 1997
- Structural characterization and alternate splicing of the gene encoding the preadipocyte EGF-like protein Pref-1Biochemistry, 1994
- Genomic imprinting in mammalian development: a parental tug-of-warTrends in Genetics, 1991
- Deletion 14q(q24.3 to q32.1) syndrome: significance of peculiar facial appearance in its diagnosis, and deletion mapping of (?1-antitrypsin)Human Genetics, 1986