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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@article{feb1669e42a64d5683ccefd3f689a0c4,
title = "TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding",
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 {\textquoteleft}infliximab{\textquoteright} 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.",
keywords = "murine polyarthritis, breeding, infliximab, refinement",
author = "Amy Naylor and Guillaume Desanti and Atif Saghir and Rowan Hardy",
year = "2017",
month = may,
day = "8",
doi = "10.1177/0023677217707985",
language = "English",
journal = "Laboratory Animals",
issn = "0023-6772",
publisher = "SAGE Publications",

}

RIS

TY - JOUR

T1 - TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding

AU - Naylor, Amy

AU - Desanti, Guillaume

AU - Saghir, Atif

AU - Hardy, Rowan

PY - 2017/5/8

Y1 - 2017/5/8

N2 - 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.

AB - 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.

KW - murine polyarthritis

KW - breeding

KW - infliximab

KW - refinement

U2 - 10.1177/0023677217707985

DO - 10.1177/0023677217707985

M3 - Article

JO - Laboratory Animals

JF - Laboratory Animals

SN - 0023-6772

ER -