title: Few alterations in clinical pathology and histopathology observed in a CYP2C18&19 humanized mice model.
abstract: BACKGROUND
  This 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).
  
  
  METHODS
  Hemizygous 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.
  
  
  RESULTS
  In males, the tissue weights were lower in tg-CYP2C18&19 than in wild-type mice for brain (p < or = 0.05), adrenal glands (p < or = 0.05) and brown fat deposits (p < or = 0.001) while the heart weight was higher (p < or = 0.001). In female tg-CYP2C18&19, the tissue weights were lower for brain (p < or = 0.001) and spleen (p < or = 0.001) compared to wild-type females. Male tg-CYP2C18&19 had increased blood glucose levels (p < or = 0.01) while females had decreased blood triglyceride levels (p < or = 0.01).
  
  
  CONCLUSIONS
  Despite 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.
authors.affiliation: Safety Assessment Sweden, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. susanne.lofgren@astrazeneca.com
authors.forename: Susanne
authors.initials: S
authors.lastname: Löfgren
authors.forename: Stina
authors.initials: S
authors.lastname: Ekman
authors.forename: Ylva
authors.initials: Y
authors.lastname: Terelius
authors.forename: Ronny
authors.initials: R
authors.lastname: Fransson-Steen
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000311:Adrenal Glands / Q000033:anatomy & histology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001774:Blood Chemical Analysis; D001786:Blood Glucose; D001921:Brain / Q000033:anatomy & histology; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D005247:Feeding Behavior; D005260:Female; D005835:Genitalia / Q000033:anatomy & histology; D006321:Heart / Q000033:anatomy & histology; D006801:Humans; D007668:Kidney / Q000033:anatomy & histology; D008099:Liver / Q000033:anatomy & histology; D008168:Lung / Q000033:anatomy & histology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D013154:Spleen / Q000033:anatomy & histology; D013950:Thymus Gland / Q000033:anatomy & histology; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D001189:Aryl Hydrocarbon Hydroxylases; C082185:CYP2C18 protein, human; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19