A transgenic mouse expressing human CYP1A2 in the pancreas.
A transgenic mouse line expressing the human cytochrome P450 CYP1A2 in the pancreas under the control of the mouse elastase promoter was established. The expression of CYP1A2 was specific to the transgenic pancreas and was not found in the control wild-type mouse pancreas. The level of CYP1A2 expressed in pancreatic microsomes from transgenic mice was comparable to that of the endogenously expressed CYP1A2 protein in the liver, as judged by western blotting analyses. Estrone metabolism was used to determine the activity of CYP1A2 expressed in the pancreas of the transgenic mouse. The transgenic pancreas exhibited almost one-third to one-half of the activity of wild-type or CYP1A2 transgenic mouse liver, whereas the wild-type pancreas demonstrated no activity. The addition of NADPH-cytochrome P450 oxidoreductase to the reaction mixture containing pancreatic microsomes from the transgenic mice did not increase the estrone metabolism activity significantly. This transgenic mouse line provides another useful tool to study human CYP1A2 and its relation to chemical toxicity and carcinogenesis.
Ueno
T
T
Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20850, USA.
Tamura
S
S
Frels
W I
WI
Shou
M
M
Gonzalez
F J
FJ
Kimura
S
S
D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D004970:Estrone / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D011994:Recombinant Proteins; D004970:Estrone; D019388:Cytochrome P-450 CYP1A2