Few alterations in clinical pathology and histopathology observed in a CYP2C18&19 humanized mice model |
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| Authors: | Susanne L?fgren Stina Ekman Ylva Terelius Ronny Fransson-Steen |
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| Institution: | 1.Safety Assessment Sweden, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden;2.Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology & Toxicology, Box 7028, SLU, S-750 07 Uppsala, Sweden;3.Medivir AB, P.O. Box 1086, S-141 22 Huddinge, Sweden |
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| Abstract: | BackgroundThis study was performed to characterize a gene-addition transgenic mouse containing a BAC (bacterial artificial chromosome) clone spanning the human CYP2C18&19 genes (tg-CYP2C18&19).MethodsHemizygous tg-CYP2C18&19, 11 week old mice were compared with wild-type littermates to obtain information regarding clinical status, clinical pathology and anatomical pathology. After one week of clinical observations, blood samples were collected, organs weighed, and tissues collected for histopathology.ResultsIn males, the tissue weights were lower in tg-CYP2C18&19 than in wild-type mice for brain (p ≤ 0.05), adrenal glands (p ≤ 0.05) and brown fat deposits (p ≤ 0.001) while the heart weight was higher (p ≤ 0.001). In female tg-CYP2C18&19, the tissue weights were lower for brain (p ≤ 0.001) and spleen (p ≤ 0.001) compared to wild-type females. Male tg-CYP2C18&19 had increased blood glucose levels (p ≤ 0.01) while females had decreased blood triglyceride levels (p ≤ 0.01).ConclusionDespite the observed alterations, tg-CYP2C18&19 did not show any macroscopic or microscopic pathology at the examined age. Hence, these hemizygous transgenic mice were considered to be viable and healthy animals. |
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