PPAR gamma is required for placental, cardiac, and adipose tissue development.
PPAR gamma is required for placental, cardiac, and adipose tissue development.
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DOI：
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发表时间：
1999
期刊：
影响因子：
16
通讯作者：
Y. Barak;M. Nelson;E. Ong;Y. Jones;P. Ruiz‐Lozano;K. Chien;A. Koder;R. Evans
中科院分区：
文献类型：
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作者：
Y. Barak;M. Nelson;E. Ong;Y. Jones;P. Ruiz‐Lozano;K. Chien;A. Koder;R. Evans
核激素受体PPAR γ促进脂肪生成和巨噬细胞分化，是治疗II型糖尿病的主要药理靶点。在这里，我们发现PPAR γ基因敲除导致两个独立的致死阶段。最初，PPAR γ缺乏干扰滋养细胞的终末分化和胎盘血管形成，导致严重的心肌变薄和E10.0死亡。通过与四倍体胚胎聚集，将PPAR γ缺失胚胎与野生型胎盘一起补充，可以纠正心脏缺陷，这暗示了以前未被认识到的发育中的心脏对功能性胎盘的依赖性。存活到足月的四倍体获救突变体表现出另一种致命的病理组合，包括脂肪营养不良和多发性出血。这些发现证实并扩展了目前已知的PPAR γ调节的生理功能谱。
The nuclear hormone receptor PPAR gamma promotes adipogenesis and macrophage differentiation and is a primary pharmacological target in the treatment of type II diabetes. Here, we show that PPAR gamma gene knockout results in two independent lethal phases. Initially, PPAR gamma deficiency interferes with terminal differentiation of the trophoblast and placental vascularization, leading to severe myocardial thinning and death by E10.0. Supplementing PPAR gamma null embryos with wild-type placentas via aggregation with tetraploid embryos corrects the cardiac defect, implicating a previously unrecognized dependence of the developing heart on a functional placenta. A tetraploid-rescued mutant surviving to term exhibited another lethal combination of pathologies, including lipodystrophy and multiple hemorrhages. These findings both confirm and expand the current known spectrum of physiological functions regulated by PPAR gamma.