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Nucleic Acids Research, 1993, Vol. 21, No. 16 3885-3891
© 1993


MOLECULAR BIOLOGY

Cloning and regulation of the rat mdr2 gene

Paul C. Brown1,2,*, Snorri S. Thorgeirsson2 and Jeffrey A. Silverman2

1National Institute of General Medical Sciences National Cancer Institute, National Institutes of Health Bethesda, MD 20892, USA 2Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health Bethesda, MD 20892, USA

*To whom correspondence should be addressed at: National Cancer Institute, Building 37, Room 3C28, 9000 Rockville Pike, Bethesda, MD 20892-0037, USA

Received February 1, 1993. Revised June 25, 1993. Accepted June 25, 1993.

We have cloned the complete cDNA encoding the rat mdr2 gene by a combination of library screening and the polymerase chain reaction. The sequence of rat mdr2 cDNA Is highly similar to other members of the mdr gene family but the Initiation of transcription, tissue distribution and regulation of expression of rat mdr2 diverge from the other Isoforms. Primer extension analysis showed rat mdr2 mRNA to have a major transcription start point at – 277 and a minor one at approximately –518. We constructed gene specific probes for rat mdr2 and mdr1b and compared the expression patterns of these two genes. The highest expression of mdr2 mRNA was In the muscle, heart, liver and spleen. Both mdr2 and 1b mRNA levels were elevated In the livers of rats treated with CCl4 or following partial hepatectomies although the time course of induction of each gene differed. Mdr1b increased by 12 to 24 hours while mdr2 did not Increase until 48 hours. Treatment of Isolated hepatocytes or RC3 cells with cyclohexlmlde did not effect mdr2 mRNA. In contrast, mdr1b expression was increased. These data suggest that rat mdr2, unlike mdr1b, is not regulated by a negative trans-acting protein factor.


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