JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Otterness, D. M.
Right arrow Articles by Weinshilboum, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Otterness, D. M.
Right arrow Articles by Weinshilboum, R. M.

Mouse thiopurine methyltransferase pharmacogenetics: monogenic inheritance

DM Otterness and RM Weinshilboum

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds such as the drug 6- mercaptopurine. In humans, TPMT activity is inherited as a monogenic trait. It would be useful if there were an animal model in which the genetic regulation of TPMT could be studied. Average TPMT activities in livers of C57BL/6J (B6) and AKR/J (AK) mice were only 17 to 29% of average activities in livers of like-sexed DBA/2J (D2) mice. Average TPMT activities in kidneys of B6 and AK mice were only 41 to 45% of average activities in kidneys of like-sexed D2 mice. Breeding experiments were performed to study the possible role of inheritance in regulating variations in TPMT activity in these mice. TPMT activities in livers and kidneys of F1 (hybrid) animals (N = 38) from D2 X B6 matings were intermediate to those in the parental strains but were closer to D2 than to B6 values, an observation that suggested partial dominance of the D2 phenotype. The results of studies of F2 (N = 107) and backcross (N = 102) animals derived from these matings were compatible with autosomal recessive inheritance of the trait of low TPMT activity in these mouse strains. Of the F2 animals, 27.1% were included in a "low" TPMT subgroup when enzyme activities in livers and kidneys were both used for phenotypic classification. TPMT activities in livers and kidneys of F1 mice (N = 40) from D2 X AK matings were also intermediate to those in the parental strains but were closer to D2 than to AK values.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 240, Issue 3, pp. 817-824, 03/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Cancer Res.Home page
C. Hartford, E. Vasquez, M. Schwab, M. J. Edick, J. E. Rehg, G. Grosveld, C.-H. Pui, W. E. Evans, and M. V. Relling
Differential Effects of Targeted Disruption of Thiopurine Methyltransferase on Mercaptopurine and Thioguanine Pharmacodynamics
Cancer Res., May 15, 2007; 67(10): 4965 - 4972.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
L. Ranjard, C. Prigent-Combaret, S. Nazaret, and B. Cournoyer
Methylation of Inorganic and Organic Selenium by the Bacterial Thiopurine Methyltransferase
J. Bacteriol., June 1, 2002; 184(11): 3146 - 3149.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.