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首页> 外文期刊>Cell cycle >Apoptosis through targeted activation of caspase 8 ('ATTAC-mice'): novel mouse models of inducible and reversible tissue ablation.
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Apoptosis through targeted activation of caspase 8 ('ATTAC-mice'): novel mouse models of inducible and reversible tissue ablation.

机译：通过半胱天冬酶8（“ ATTAC-小鼠”）的有针对性的激活而引起的细胞凋亡：诱导型和可逆性组织消融的新型小鼠模型。

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Recent studies identifying obesity as a significant and increasingly more common cause of morbidity and mortality have intensified research efforts aimed at increasing our understanding of adipose tissue biology. These efforts have culminated in the discovery of several adipokines, or adipose tissue-derived hormones, that have been implicated in the regulation of multiple physiological functions, as well as the realization that adipose tissue dysfunction plays an important role in the pathogenesis of diseases such as obesity and diabetes. To better understand the role of adipose tissue in these physiological/pathological events, several studies have employed transgenic strategies to eliminate adipose tissue. However, these mouse models of congenital lipoatrophy/lipodystrophy exhibit severe metabolic and somatic cell dysfunction. To circumvent this limitation, we have designed and characterized the first inducible fatless mouse. The FAT-ATTAC mouse is a transgenic model whereby expression of a myristoylated caspase 8-FKBP fusion protein enables selective ablation of adipocytes via induction of apoptosis that occurs upon treatment with a chemical dimerizer. The FAT-ATTAC mouse model not only has the advantage that adipocyte ablation be induced at any time during development, but it is also fully reversible, as adipose tissue regenerates after cessation of dimerizer treatment. The inducibility of this fatless mouse model holds potential for revealing novel physiological roles for adipose tissue as well as its contribution to the etiology and pathogenesis of various disease states. Here we describe several ongoing areas of research employing the FAT-ATTAC mouse; in addition we describe potential uses of the targeted transgenic apoptotic approach to study other cell types of interest.
机译：最近的研究表明，肥胖是发病率和死亡率的重要原因，并且越来越普遍。肥胖的研究力度加大，旨在增进我们对脂肪组织生物学的了解。这些努力最终导致发现了几种脂肪因子或脂肪组织衍生的激素，这些激素与多种生理功能的调节有关，并认识到脂肪组织功能障碍在诸如以下疾病的发病机理中起着重要作用。肥胖和糖尿病。为了更好地了解脂肪组织在这些生理/病理事件中的作用，数项研究采用了转基因策略来消除脂肪组织。但是，这些先天性脂肪萎缩/脂肪营养不良的小鼠模型表现出严重的代谢和体细胞功能障碍。为了避免这种局限性，我们设计并鉴定了第一只诱导型无脂肪小鼠。 FAT-ATTAC小鼠是一种转基因模型，其中，肉豆蔻酰化的半胱天冬酶8-FKBP融合蛋白的表达能够通过诱导凋亡来选择性切除脂肪细胞，而凋亡是在用化学二聚体处理后发生的。 FAT-ATTAC小鼠模型不仅具有在发育过程中随时诱导脂肪细胞消融的优势，而且由于脂肪组织在停止二聚体治疗后再生，因此是完全可逆的。这种无脂肪小鼠模型的可诱导性具有揭示脂肪组织新的生理作用及其对各种疾病状态的病因和发病机理的贡献的潜力。在这里，我们描述了使用FAT-ATTAC鼠标进行的几个研究领域。此外，我们描述了靶向转基因凋亡方法在研究其他感兴趣细胞类型中的潜在用途。

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