Inducible ablation of adipocytes in adult transgenic mice expressing the E. coli nitroreductase gene

in Journal of Endocrinology
Authors:
R Felmer
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,
W Cui
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AJ Clark
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DOI:
https://doi.org/10.1677/joe.0.1750487
Volume/Issue:
Volume 175: Issue 2
Article Type:
Other
Page Range:
487–498
Online Publication Date:
01 Nov 2002
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We describe the use of an enzyme prodrug system based on E. coli nitroreductase (NTR) to achieve the specific ablation of adipose tissue. Transgenic mice expressing the NTR gene specifically in the adipose tissue were generated using the adipocyte specific promoter aP2. After treatment with the prodrug CB1954 these mice showed extensive cell depletion in all fat depots; this was directly correlated to both the dose of prodrug and the levels of NTR expression. Higher doses of CB1954 resulted in complete disappearance of visible adipose stores in some transgenic mice. These mice exhibited an impaired ability to thermoregulate body temperature. Lower doses of CB1954 resulted in a partial reduction of the adipose tissue leaving non-expressing cells that escape ablation. These animals show normal levels of blood glucose and triglycerides but have reduced leptin levels. After 30 days they were able to regenerate the fat depots and leptin levels returned to normal but, interestingly, no NTR-expressing cells were detectable. The present model provides a new approach to manipulate the number of adipocytes at different stages of mouse development and provides a new system for the study of fat metabolism especially in abnormal conditions such as obesity and its modulation through manipulation of the target cell population.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Page(s):
12
Article Type:
Other
Print Publication Date:
01 Nov 2002
Online Publication Date:
01 Nov 2002