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TNF? depleting therapy improves fertility and animal welfare in TNF?-driven transgenic models of polyarthritis when administered in their routine breeding.

ABSTRACT: Transgenic tumour necrosis factor alpha (TNF?)-driven models of polyarthritis such as the TNF^?ARE 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 TNF? depleting therapy 'infliximab' might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNF^?ARE 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 TNF^?ARE males prior to, and following, regular introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNF^?ARE males receiving infliximab (control 6.6 arbitrary units [AU]?±?0.88 versus infliximab 4.4 AU?±?1.4; P??ARE males receiving infliximab injections sired more litters over their breeding lifespan (control 1.69?±?0.22 versus infliximab 3.00?±?0.19; P??ARE 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 TNF^?ARE animals. In addition, we have shown that infliximab is highly efficacious in improving breeding behaviour and increasing the number of litters sired by TNF^?ARE males.

SUBMITTER: Naylor AJ

PROVIDER: S-EPMC5802519 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding.

Naylor Amy J AJ Desanti Guillaume G Saghir Atif N AN Hardy Rowan S RS

Laboratory animals 20170508 1

Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNF<sup>ΔARE</sup> 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 TNFα depleting therapy 'infliximab' might represent a significant refinement in routine breeding. Clinical scores of joint i ...[more]

PMID: 28480797

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Dataset Information

TNF? depleting therapy improves fertility and animal welfare in TNF?-driven transgenic models of polyarthritis when administered in their routine breeding.

Publications

TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding.

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