Few alterations in clinical pathology and histopathology observed in a CYP2C1819 humanized mice model.docVIP

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Few alterations in clinical pathology and histopathology observed in a CYP2C1819 humanized mice model.doc

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FewalterationsinclinicalpathologyandhistopathologyobservedinaCYP2C18

Acta Veterinaria Scandinavica BioMedCentral Research Open Access Few alterations in clinical pathology and histopathology observed in a CYP2C1819 humanized mice model Susanne L?fgren*1, Stina Ekman2, Ylva Terelius3 and Ronny Fransson-Steen1 Address: 1Safety Assessment Sweden, AstraZeneca RD S?dert?lje, S-151 85 S?dert?lje, Sweden, 2Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology Toxicology, Box 7028, SLU, S-750 07 Uppsala, Sweden and 3Medivir AB, P.O. Box 1086, S-141 22 Huddinge, Sweden Email: Susanne L?fgren* - susanne.lofgren@; Stina Ekman - stina.ekman@bvf.slu.se; Ylva Terelius - Ylva.Terelius@; Ronny Fransson-Steen - ronny.fransson-steen@ * Corresponding author Published: 27 November 2008 Received: 2 July 2008 Accepted: 27 November 2008 Acta Veterinaria Scandinavica 2008, 50:47 doi:10.1186/1751-0147-50-47 This article is available from: /content/50/1/47 ? 2008 L?fgren et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: This study was performed to characterize a gene-addition transgenic mouse containing a BAC (bacterial artificial chromosome) clone spanning the human CYP2C1819 genes (tg-CYP2C1819). Methods: Hemizygous tg-CYP2C1819, 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. Results: In males, the tissue weights were lower in tg-CYP2C1819 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