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Abstract
Transgenic tumour necrosis factor alpha (TNFa)-driven models of polyarthritis such as the TNFARE mouse
have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans.
Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment
to breeding management. We examined whether TNFa depleting therapy ‘infliximab’ might represent a
significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNFARE
males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection. Joint histology
and bone morphology were assessed by histological analysis and micro-computed tomography (CT), respectively.
Analysis of breeding was examined retrospectively in TNFARE males prior to, and following, regular
introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNFARE males
receiving infliximab (control 6.6 arbitrary units [AU]0.88 versus infliximab 4.4 AU1.4; P<0.05), while
measures of pannus invasion and bone erosion by histology and micro-CT were markedly reduced. In the
breeding groups, TNFARE males receiving infliximab injections sired more litters over their breeding lifespan
(control 1.690.22 versus infliximab 3.000.19; P<0.005). Furthermore, prior to infliximab, TNFARE males
had a 26% risk of failing to sire any litters. This was reduced to 7% after the introduction of infliximab. This
study is the first to report that regular administration of infliximab is effective at suppressing disease activity
and improving animal welfare in TNFARE animals. In addition, we have shown that infliximab is highly efficacious
in improving breeding behaviour and increasing the number of litters sired by TNFARE males.
Original language | English |
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Journal | Laboratory Animals |
Early online date | 8 May 2017 |
DOIs | |
Publication status | E-pub ahead of print - 8 May 2017 |
Keywords
- murine polyarthritis
- breeding
- infliximab
- refinement
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Dive into the research topics of 'TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding'. Together they form a unique fingerprint.Projects
- 1 Finished
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Mechanisms Underlying Inflammation Associated Muscle Loss
Raza, K. (Principal Investigator), Lavery, G. (Co-Investigator), Buckley, C. (Co-Investigator) & Stewart, P. (Co-Investigator)
1/06/12 → 31/05/16
Project: Research