Mice lacking paternally expressed Pref-1/Dlk1 display growth retardation and accelerated adiposity.
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.
Moon
Yang Soo
YS
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Smas
Cynthia M
CM
Lee
Kichoon
K
Villena
Josep A
JA
Kim
Kee-Hong
KH
Yun
Eun Jun
EJ
Sul
Hei Sook
HS
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D000818:Animals; D016569:Blepharophimosis / Q000235:genetics; D001835:Body Weight; D002135:Calcium-Binding Proteins; D004195:Disease Models, Animal; D005220:Fathers; D018392:Genomic Imprinting; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D036341:Intercellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009035:Mothers; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics; D012272:Ribs / Q000002:abnormalities; D024182:Uniparental Disomy / Q000235:genetics* / Q000473:pathology
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins