Characterization of adiposity and metabolism in Lmna-deficient mice
Characterization of adiposity and metabolism in Lmna-deficient mice
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DOI：
10.1006/bbrc.2002.6466
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发表时间：
2002-03-01
影响因子：
3.1
通讯作者：
Reitman, ML
中科院分区：
文献类型：
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作者：
Cutler, DA;Sullivan, T;Reitman, ML
邓尼根氏家族性部分脂肪营养不良症（FPLD）是一种常染色体显性遗传病，其特征是区域性脂肪减少和胰岛素抵抗。FPLD是由编码核膜中间丝的LMNA基因突变引起的。不同的LMNA突变可引起emry - dreifuss肌营养不良和/或扩张型心肌病。目前尚不清楚LMNA突变如何引起任何疾病表型。在这里，我们测量了Lmna-/-和+/-小鼠的身体和代谢特征，以确定它们作为FPLD模型的实用性。早死于肌肉萎缩症的Lmna-/-小鼠脂肪较少，但未表现出FPLD的胰岛素抵抗特征。Lmna+/-小鼠，尽管用高脂肪饮食治疗，并没有减少脂肪储存或FPLD的代谢特征。我们还表明，在小鼠中，Lmna转录本在肌肉和脂肪组织中高水平表达，但不随身体区域或性别而变化。总之，Lmna+/-和-/-小鼠不会模仿Dunnigan's FPLD，并且层粘胶蛋白A和C的差异表达似乎不会导致性别或组织特异性Lmna表型。
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.