A mutant rat strain deficient in induction of a phenobarbital-inducible form of cytochrome P-450 in liver microsomes.
Two phenobarbital-inducible forms of cytochrome P-450, P-450(PB-1), and P-450(PB-4), were purified from the liver microsomes of phenobarbital-treated rats and identified with P-450b and P-450e, respectively. It was found, however, that the content of P-450(PB-4) in the liver microsomes of a strain of SD rat, Qdj:SD, was very low even after phenobarbital-induction. The levels of the mRNAs for P-450(PB-1) and P-450(PB-4) were separately determined using Northern blot hybridization with specific oligonucleotide probes. It was found that the level of P-450(PB-4) mRNA in the livers of phenobarbital-treated Qdj:SD rats was much lower than that of phenobarbital-treated Slc:SD rats. Slc:SD rats are widely used in Japanese laboratories. Genetic analysis using the crossbred animals between Qdj:SD and Slc:SD rats showed that the low expression of P-450(PB-4) in Qdj:SD rats is a recessive trait and is caused by a single gene mutation. However, no difference in the 5' flanking region in P-450(PB-4) gene was found between Qdj:SD rats and Slc:SD rats.
Hashimoto
T
T
Department of Biology, Faculty of Science, Kyushu University, Fukuoka.
Matsumoto
T
T
Nishizawa
M
M
Kawabata
S
S
Morohashi
K
K
Handa
S
S
Omura
T
T
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D007120:Immunochemistry; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D004262:DNA Restriction Enzymes; D010634:Phenobarbital