Few alterations in clinical pathology and histopathology observed in a CYP2C18&19 humanized mice model.
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.
Löfgren
Susanne
S
Safety Assessment Sweden, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. susanne.lofgren@astrazeneca.com
Ekman
Stina
S
Terelius
Ylva
Y
Fransson-Steen
Ronny
R
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
D001786:Blood Glucose; D001189:Aryl Hydrocarbon Hydroxylases; C082185:CYP2C18 protein, human; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19