Construction nearby animal houses has sporadically been reported to affect various aspects of animal health. Most of the reports have focussed on the impact on stress hormone levels and the hypersensitivity of animals relative to humans. There has also been an anecdotal report on the impact of construction on autoimmune diabetes in NOD mice. Here, we describe that nearby construction significantly impedes the progression to overt diabetes in female NOD mice offspring. We demonstrate that this was not due to a genetic drift or to particularities associated with our specific mouse colony. Interestingly, although the glycemia levels remained low in mice born from mothers subject to construction stress during gestation, we detected an active autoimmune reaction towards pancreatic islet cells, as measured by both the degree of insulitis and the presence of insulin autoantibody levels in the serum. These results suggest that the external stress imposed during embryonic development does not prevent but significantly delays the autoimmune process. Together, our findings emphasize the impact of surrounding factors during in vivo studies and are in agreement with the hypothesis that both environmental and genetic cues contribute to autoimmune diabetes development. 1. Introduction The NOD mouse was developed in the 1970s in Japan and has since become the animal model of choice to investigate the genetic, cellular, and molecular mechanisms involved in the development of autoimmune diabetes [1]. This inbred strain spontaneously develops an autoimmune reaction towards pancreatic islet antigens, destroying the insulin-producing pancreatic beta cells. The spontaneous disease process in the NOD mouse parallels that observed in humans and, consequently, the NOD mouse model provides an important tool to dissect and better understand the complex pathophysiological process leading to disease onset [2, 3]. Two main factors are known to contribute to disease susceptibility of this complex trait, namely, genetic and environmental factors. First, autoimmune diabetes is a complex genetic trait, with over 50 genetic loci contributing to disease susceptibility [4, 5]. Interestingly, a direct parallel can be made between most of the diabetes susceptibility genetic risk factors currently identified in humans and mice [6]. However, a notable difference is that although the prevalence of autoimmune diabetes in humans is not influenced by gender, the incidence in female NOD mice is consistently higher than that of male mice [1]. Nevertheless, the NOD strain constitutes a valid model to
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