No self-injurious behavior was found in HPRT-deficient mice treated with 9-ethyladenine.
It has been reported that 9-ethyladenine (9-EA) is an efficient inhibitor of APRT (adenine phosphoribosyltransferase) and that its administration causes self-injurious behavior (Lesch-Nyhan Syndrome-like symptoms) in HPRT (hypoxanthine-guanine phosphoribosyltransferase)-deficient mice. In contrast, we found neither any self-injurious behavior (SIB), such as visible injury or hair loss, nor any apparent decrease in APRT activity in HPRT-deficient mice treated with 9-EA. We also found that 9-EA has little irreversible or competitive inhibitory effect on APRT in vitro, even at a concentration of 10(-2) M. In light of the negative finding of SIB in APRT/HPRT double-deficient mice, it seems unlikely that SIB in HPRT-deficient mice is caused by lowered APRT activity. It is concluded that 9-EA is not a sufficient APRT inhibitor and cannot be used in experiments that mimic lowered APRT status in an animal model.
Edamura
K
K
Life Science Research Laboratory, Japan Tobacco Inc., Yokohama, Kanagawa.
Sasai
H
H
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002457:Cell Extracts; D004195:Disease Models, Animal; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007926:Lesch-Nyhan Syndrome / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D016728:Self-Injurious Behavior
D002457:Cell Extracts; C001172:9-ethyladenine; D007041:Hypoxanthine Phosphoribosyltransferase; D000225:Adenine