Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin.
Mice carrying mutations in the fatty liver dystrophy (fld) gene have features of human lipodystrophy, a genetically heterogeneous group of disorders characterized by loss of body fat, fatty liver, hypertriglyceridemia and insulin resistance. Through positional cloning, we have isolated the gene responsible and characterized two independent mutant alleles, fld and fld(2J). The gene (Lpin1) encodes a novel nuclear protein which we have named lipin. Consistent with the observed reduction of adipose tissue mass in fld and fld(2J)mice, wild-type Lpin1 mRNA is expressed at high levels in adipose tissue and is induced during differentiation of 3T3-L1 pre-adipocytes. Our results indicate that lipin is required for normal adipose tissue development, and provide a candidate gene for human lipodystrophy. Lipin defines a novel family of nuclear proteins containing at least three members in mammalian species, and homologs in distantly related organisms from human to yeast.
Péterfy
M
M
Department of Medicine, University of California, Los Angeles, California, USA.
Phan
J
J
Xu
P
P
Reue
K
K
D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance / Q000235:genetics; D020738:Leptin / Q000032:analysis; D008060:Lipodystrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D010711:Phosphatidate Phosphatase; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D021101:Radiation Hybrid Mapping; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D020738:Leptin; D009687:Nuclear Proteins; D012333:RNA, Messenger; C485999:LPIN1 protein, human; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase