title: Characterization of adiposity and metabolism in Lmna-deficient mice.
abstract: Dunnigan's Familial Partial Lipodystrophy (FPLD) is an autosomal dominant disease characterized by regional fat loss and insulin resistance. FPLD is caused by mutations in the LMNA gene, which encodes intermediate filaments of the nuclear lamina. Different LMNA mutations cause Emery-Dreifuss muscular dystrophy and/or a dilated cardiomyopathy. It is not known how LMNA mutations cause any of the disease phenotypes. Here we measure physical and metabolic characteristics of Lmna-/- and +/- mice to determine their usefulness as models for FPLD. Lmna-/- mice, which die prematurely of muscular dystrophy, have little fat, but do not show the insulin resistance characteristic of FPLD. Lmna+/- mice, despite treatment with a high fat diet, do not have decreased fat stores or metabolic features of FPLD. We also show, in mice, that Lmna transcripts are expressed at high levels in muscle and adipose tissue, but do not vary by body region or sex. In conclusion, Lmna+/- and -/- mice do not mimic Dunnigan's FPLD, and differential expression of lamins A and C does not appear to contribute to sex- or tissue-specific LMNA phenotypes.
authors.affiliation: Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1770, USA.
authors.forename: Dedra A
authors.initials: DA
authors.lastname: Cutler
authors.forename: Teresa
authors.initials: T
authors.lastname: Sullivan
authors.forename: Bernice
authors.initials: B
authors.lastname: Marcus-Samuels
authors.forename: Colin L
authors.initials: CL
authors.lastname: Stewart
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004195:Disease Models, Animal; D004435:Eating; D005260:Female; D007328:Insulin / Q000097:blood; D034882:Lamins; D008060:Lipodystrophy / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D008297:Male; D051379:Mice / Q000235:genetics*; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000209:etiology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D012737:Sex Factors; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D034882:Lamins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014280:Triglycerides