HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome.
Complete hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency in humans results in the Lesch-Nyhan syndrome which is characterized, among other features, by compulsive self-injurious behavior. HPRT-deficient mice generated using mouse embryonic stem cells exhibit none of the behavioral symptoms associated with the Lesch-Nyhan syndrome. Administration of drugs that inhibit adenine phosphoribosyltransferase (APRT) in HPRT-deficient mice has produced the suggestion that deficiency of APRT in combination with HPRT-deficiency in mice may lead to self-mutilation behavior [C.L. Wu and D.W. Melton (1993) Nature Genet. 3, 235-240]. To test this proposition, we bred HPRT-APRT-deficient mice. Although the doubly-deficient mice excrete adenine and its highly insoluble derivative, 2,8-dihydroxyadenine, which are also associated with human APRT deficiency, additional abnormalities or any self-injurious behavior were not detected. Thus, APRT-HPRT-deficient mice, which are devoid of any purine salvage pathways, show no novel phenotype and are not a model for the behavioral abnormalities associated with the Lesch-Nyhan syndrome as previously suggested.
Engle
S J
SJ
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251, USA.
Womer
D E
DE
Davies
P M
PM
Boivin
G
G
Sahota
A
A
Simmonds
H A
HA
Stambrook
P J
PJ
Tischfield
J A
JA
D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007926:Lesch-Nyhan Syndrome; D051379:Mice
D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase