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 journalArticle

20 Citations (Scopus)

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
StatePublished - Sep 2005

Fingerprint

Ablation
Adipose Tissue
Chemical activation
Tissue
Apoptosis
Adipocytes
Obesity
Tacrolimus Binding Proteins
Lipodystrophy
Withholding Treatment
Adipokines
Caspase 8
Medical problems
Research
Fusion reactions
Hormones
Morbidity
Mortality
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Apoptosis through targeted activation of caspase8 ("ATTAC-mice") : Novel mouse models of inducible and reversible tissue ablation. / Trujillo, Maria E.; Pajvani, Utpal B.; Scherer, Philipp E.

In: Cell Cycle, Vol. 4, No. 9, 09.2005, p. 1141-1145.

Research output: Contribution to journalArticle

@article{50e9267daac64982aed34b14eb465883,
title = "Apoptosis through targeted activation of caspase8 ({"}ATTAC-mice{"}): Novel mouse models of inducible and reversible tissue ablation",
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.",
keywords = "Adipocyte, Adipogenesis, Adipohine, Angiogenesis, Apoptosis, Caspase, Fatless, Lipoatrophy, Lipodystrophy",
author = "Trujillo, {Maria E.} and Pajvani, {Utpal B.} and Scherer, {Philipp E.}",
year = "2005",
month = "9",
language = "English (US)",
volume = "4",
pages = "1141--1145",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "9",

}

TY - JOUR

T1 - Apoptosis through targeted activation of caspase8 ("ATTAC-mice")

T2 - Novel mouse models of inducible and reversible tissue ablation

AU - Trujillo, Maria E.

AU - Pajvani, Utpal B.

AU - Scherer, Philipp E.

PY - 2005/9

Y1 - 2005/9

N2 - 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.

AB - 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.

KW - Adipocyte

KW - Adipogenesis

KW - Adipohine

KW - Angiogenesis

KW - Apoptosis

KW - Caspase

KW - Fatless

KW - Lipoatrophy

KW - Lipodystrophy

UR - http://www.scopus.com/inward/record.url?scp=25444505003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25444505003&partnerID=8YFLogxK

M3 - Article

C2 - 16096375

AN - SCOPUS:25444505003

VL - 4

SP - 1141

EP - 1145

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 9

ER -