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Fatal gastric distension in a gold thioglucose mouse model of obesity.

Abstract
This case report addresses the problem of underreporting negative results and adverse side effects in animal testing. We present our findings regarding a hyperphagic mouse model associated with unforeseen high mortality. The results outline the necessity of reporting detailed information in the literature to avoid duplication. Obese mouse models are essential in the study of obesity, metabolic syndrome and diabetes mellitus. An experimental model of obesity can be induced by the administration of gold thioglucose (GTG). After transcending the blood-brain barrier, the GTG molecule interacts with regions of the ventromedial hypothalamus, thereby primarily targeting glucose-sensitive neurons. When these neurons are impaired, mice become insensitive to the satiety effects of glucose and develop hyperphagia. In a pilot study for optimising dosage and body weight development, C57BL/6 mice were treated with GTG (0.5 mg/g body weight) or saline, respectively. Animals were provided a physiological amount of standard diet (5 g per animal) for the first 24 hours after treatment to prevent gastric dilatation. Within 24 hours after GTG injection, all GTG-treated animals died of gastric overload and subsequent circulatory shock. Animals developed severe attacks of hyperphagia, and as the amount of provided chow was restricted, mice exhibited unforeseen pica and ingested bedding material. These observations strongly suggest that restricted feeding is contraindicated concerning GTG application. Presumably, the impulse of excessive food intake was a strong driving force. Therefore, the actual degree of suffering in the GTG-induced model of hyperphagia should be revised from moderate to severe.
AuthorsTina Nitezki, Burkhard Kleuser, Stephanie Krämer
JournalLaboratory animals (Lab Anim) Vol. 53 Issue 1 Pg. 89-94 (Feb 2019) ISSN: 1758-1117 [Electronic] England
PMID30290722 (Publication Type: Case Reports, Journal Article)
Chemical References
  • Blood Glucose
  • Aurothioglucose
Topics
  • Animals
  • Aurothioglucose (administration & dosage)
  • Blood Glucose (metabolism)
  • Disease Models, Animal
  • Eating
  • Fatal Outcome
  • Gastric Dilatation (etiology)
  • Hyperphagia (physiopathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Pica (chemically induced, physiopathology)
  • Pilot Projects

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