Species: Mouse Strain/breeder: Taconic Farms (USA) Sex: Male Age: 10 weeks Study type: None Treatment: None Animal status: Sacrificed Clinical findings: Soft sticky faeces, body weight loss, hunched posture, lethargic, piloerection, dyspnea Organ(s): Colon, Ileum Macroscopic finding(s): Thickened colon, enlarged mesenteric lymph nodes Staining: H&E

Fig. 1 (95k) Fig. 2 (85k)

Abstract

J-L. LE NET¹, K.H. BANNER², A. POPOVIC² and C. CATTANEO¹

¹Pfizer Global R & D, Amboise Laboratories, BP 109, 37401 Amboise Cedex, France
²Pfizer Global R & D, Sandwich, England

Key words: colon, transgenic mice, spontaneous colitis

Mdr1a-deficient mice lack P-glycoprotein, a membrane efflux pump expressed in several cell types including intestinal epithelial cells. They are used in drug metabolism studies for intestinal absorption and brain penetration of drugs. Following a 3-week acclimatisation period within our facilities, most of the mice developed clinical signs of colitis such as production of soft sticky faeces and loss of body weight. At necropsy, thickening of the colon/rectum mucosa correlated with increased colon/rectum weight. Epithelial cell hyperplasia (increased crypt length, loss of goblet cells and dysregulated epithelial cell growth), mucosal infiltration with macrophages, lymphocytes and neutrophils, crypt micro-abscesses and ulcerations were the main histological findings. Mdr1a-deficient mice could be a useful animal model for ulcerative colitis, an inflammatory bowel disease in humans.