N-acetyltransferase 2 activity and folate levels.
OBJECTIVE
To determine whether increased N-acetyltransferase (NAT) activity might have a toxic effect during development and an influence on folate levels since previous work has shown that only low levels of exogenous NAT can be achieved in constitutionally transgenic mice (Cao et al. 2005).


METHODS
A human NAT1 tet-inducible construct was used that would not be expressed until the inducer was delivered. Human NAT1 cDNA was cloned into pTRE2 and injected into mouse oocytes. Two transgenic lines were crossed to mouse line TgN(rtTahCMV)4Uh containing the CMV promoted "tet(on)". Measurements of red blood cell folate levels in inbred strains of mice were performed.


RESULTS
Only low levels of human NAT1 could be achieved in kidney (highly responsive in other studies) whether the inducer, doxycycline, was given by gavage or in drinking water. An inverse correlation of folate levels with Nat2 enzyme activity was found.


CONCLUSIONS
Since increasing NAT1 activity decreases folate in at least one tissue, the detrimental effect of expression of human NAT1 in combination with endogenous mouse Nat2 may be a consequence of increased catabolism of folate.
Cao
Wen
W
Department of Pediatrics, University of Arizona, Tucson, AZ 85724-5073, USA.
Strnatka
Diana
D
McQueen
Charlene A
CA
Hunter
Robert J
RJ
Erickson
Robert P
RP
D000107:Acetylation; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003001:Cloning, Molecular; D003587:Cytomegalovirus / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000378:metabolism; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013045:Species Specificity; D019076:Transgenes
D007527:Isoenzymes; D005492:Folic Acid; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C524206:Nat2 enzyme, mouse; D004318:Doxycycline