Characterization of metallothionein-I-transgenic mice.
A metallothionein-I-transgenic mouse strain (MT-TG) was characterized to determine whether they would be suitable to study the functions of this protein. MT-TG mice were visually indistinguishable from nontransgenic littermate controls, but had 10- to 20-fold higher basal levels of MT protein in pancreas, liver, and stomach, as well as 2- to 6-fold higher MT protein levels in other organs (kidney, intestine, uterus, testes, spleen, heart, and lung) than control mice, as determined by the Cd/hemoglobin assay. The MT-TG mice had 50% more Zn in liver and 300% more Zn in pancreas than control mice. Interestingly, female MT-TG mice have 4- to 5-fold higher MT levels in liver than those of males. To determine whether MT can be further increased by well-known MT inducers, control and MT-TG mice were given Zn (200 mumol/kg), Cd (20 mumol/kg), or diethyl maleate (DEM, 5 mmol/kg), and tissue MT concentrations were measured 24 hr later. MT-TG mice responded to MT inducers in a manner similar to control mice. The hepatic antioxidant components (glutathione (GSH), GSH-peroxidase, GSH-reductase, GSH S-transferase, superoxide dismutase, DT-diaphorase, and catalase) of MT-TG mice were not different from those of controls. The cytochrome P450 enzymes (total P450, b5, NADPH cytochrome c reductase) were normal in these MT-TG mice. The activities of CYP1A, CYP2B, and CYP2E enzymes in MT-TG mice were also similar to those of controls, as determined by ethoxy- and pentoxyresorufin O-dealkylation and chlorzoxazone 6-hydroxylation. Thus, MT-TG mice appear to be a good model for studying functions of MT.
Iszard
M B
MB
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Liu
J
J
Liu
Y
Y
Dalton
T
T
Andrews
G K
GK
Palmiter
R D
RD
Klaassen
C D
CD
D000818:Animals; D002104:Cadmium / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism; D005260:Female; D005835:Genitalia / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D015032:Zinc / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity
D006454:Hemoglobins; D007527:Isoenzymes; D008298:Maleates; D002104:Cadmium; D003577:Cytochrome P-450 Enzyme System; D008668:Metallothionein; C014476:diethyl maleate; D015032:Zinc