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Mice lacking paternally expressed Pref-1/Dlk1 display growth retardation and accelerated adiposity
Yang Soo Moon1, Cynthia M Smas, Kichoon Lee
1Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Insights
Preadipocyte factor 1 (Pref-1/Dlk1) is a paternally expressed gene crucial for normal development and adipose tissue homeostasis. Its absence in knockout mice leads to growth retardation, obesity, and developmental abnormalities, suggesting its role in human genetic disorders.
Area of Science:
- Genetics
- Developmental Biology
- Endocrinology
Background:
- Preadipocyte factor 1 (Pref-1/Dlk1) inhibits adipocyte differentiation.
- Pref-1/Dlk1 is a paternally expressed imprinted gene at human chromosome 14q32.
- Misexpression of imprinted genes on chromosome 14 is linked to congenital disorders.
Purpose of the Study:
- To investigate the role of Pref-1 in growth and in vivo adipogenesis.
- To determine Pref-1's contribution to maternal uniparental disomy (mUPD).
Main Methods:
- Generation of Pref-1 knockout mice.
- Phenotypic analysis of Pref-1-null mice and heterozygotes with paternally or maternally inherited null alleles.
Main Results:
- Pref-1-null mice exhibit growth retardation, obesity, blepharophimosis, skeletal malformations, and increased serum lipids.
- Phenotypes were observed in heterozygotes with a paternally inherited null allele, but not with a maternally inherited one.
- Pref-1 is confirmed as paternally expressed and essential for normal development and adipose tissue mass homeostasis.
Conclusions:
- Pref-1 plays a critical role in mammalian development and metabolic regulation.
- Pref-1 is likely responsible for symptoms associated with mouse mUPD12 and human mUPD14.
- Pref-1-null mice serve as a valuable model for studying obesity and pathologies related to human mUPD14.
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.