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Table 1 Overview of transgenic reporter mice available for studies of inflammation

From: Molecular imaging of transcriptional regulation during inflammation

Regulatory elements of transgenic mice#

Reporter gene

Method

Features of the transgenic mice

Three NF-κB sites* separated by linker sequences (14 to 25 bp)

[32, 35, 47, 48, 53, 65–68]

Fluc (Firefly luciferase)

Pronuclear injection

In vivo imaging. Short half-life of reporter. Good induction. Used in numerous disease models. Distinct visualization of lymph nodes.

Difficult to assess single cells

Three NF-κB sites* separated by linker sequences (14 to 25 bp) Insulator sequences flank the transgene [40, 49, 51, 54, 69–76]

Fluc

Pronuclear injection

In vivo imaging. Short half-life of reporter. Insulators protect transgene against genomic interference. Used in many disease models.

Difficult to assess single cells.

Six NF-κB sites* separated by four bp. Bi-directional expression of two reporter genes

[77]

Fluc dEGFP

Pronuclear injection

In vivo imaging and detection of dEGFP in single cells. Short half-life of both reporters. Used in a brain ischemia model.

Weak dEGFP signal. Need antibodies for detection.

HIV-1 LTR with two NF-κB sites* and three Sp1 sites [31, 36, 38, 41, 52, 78–82]

Fluc

Pronuclear injection

In vivo imaging. Short half-life of reporter. Good induction. Used in various disease models mainly to study lung pathology.

Difficult to assess single cells.

HIV-1 LTR with two NF-κB sites* and three Sp1 sites

[37]

EGFP/Fluc

fusion protein

Pronuclear injection

In vivo imaging. EGFP signal detected in isolated macrophages. Short half-life of both reporters. Good induction.

Need antibodies to detect EGFP in sections.

Two NF-κB sites* [83–86]

Fluc

Pronuclear injection

Good induction. Successfully used to study T-cell regulation.

No demonstration of in vivo imaging.

Five NF-κB sites *[87]

Fluc

Pronuclear injection

In vivo imaging. Short half-life of reporter.

Used in only one study.

Three NF-κB sites* [88]

EGFP

Site specific in HPRT-locus

Signals detected from single cells and whole organs. Site specific integration prevents influence from regulatory elements outside the transgene.

In vivo imaging not shown. Stable version of EGFP complicates assessment of dynamic NF-κB regulation.

Twelve Smad 2/3 binding sites [55, 89, 90].

Fluc

Pronuclear injection

In vivo imaging. Used to study TGFβ signaling and response to injury, particularly in brain.

Difficult to assess single cells.

iNOS-promoter fragment

(1.24 kb) [57]

Fluc

Pronuclear injection

In vivo imaging. Reflects iNOS mRNA in liver. Sensitive to pro- and anti-inflammatory agents.

Used in only one study.

IκBα-promoter fragment

(11.0 kb) [58]

Fluc

Pronuclear injection

In vivo imaging. Luciferase activity reflects IκBα mRNA in liver.

Used in only one study.

SAA1-promoter fragment (7.7 kb) [59]

Fluc

Pronuclear injection

In vivo imaging. Luciferase activity reflects SAA1 mRNA in liver and protein in serum. Demonstrated in an acute arthritis model.

Used in only one study.

GADD45β-promoter fragment (10.5 kb) [60]

Fluc

Pronuclear injection

In vivo imaging. Reflects GADD45β mRNA in multiple organs. Used to study effects of various stressful insults (inflammation, oxidative stress, toxins).

Used in one study.

COX-2-promoter (endogenous) [91–93]

Fluc

Knock-in in the COX2 gene

In vivo imaging. Correlation between luciferase and COX-2 protein levels in multiple organs. Knock-in reflects endogenous promoter activity.

  1. #Include most relevant references where the models have been used.
  2. *Sequence of the NF-κB binding site: 5'-GGGACTTTCC-3'. This sequence is found in numerous NF-κB regulated promoters including immunoglobulin κ light chain and HIV LTR, and it is used in all NF-κB reporter mice generated up to now.