Apoptosis through targeted activation of caspase8 ("ATTAC-mice"): Novel mouse models of inducible and reversible tissue ablation

Maria E. Trujillo, Utpal B. Pajvani, Philipp E. Scherer

Research output: Contribution to journalReview article

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1141-1145
Number of pages5
JournalCell Cycle
Volume4
Issue number9
DOIs
StatePublished - Sep 2005

Keywords

  • Adipocyte
  • Adipogenesis
  • Adipohine
  • Angiogenesis
  • Apoptosis
  • Caspase
  • Fatless
  • Lipoatrophy
  • Lipodystrophy

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Apoptosis through targeted activation of caspase8 ("ATTAC-mice"): Novel mouse models of inducible and reversible tissue ablation'. Together they form a unique fingerprint.

  • Cite this