Tissue- and gender-specific expression of N-acetyltransferase 2 (NAT2*) during development of the outbred mouse strain CD-1

The human N-acetyltransferase (Nat2) genetic polymorphisms have been modele d in mouse strains. We determined the phenotype and genotype of the N-acety ltransferase 2 (Nat2*) gene among outbred CD-1 mice and found a mixed popul ation of heterozygous and rapid and slow homozygous genotypes. Phenotypes d etermined with p-aminobenzoic acid demonstrated complete concordance of slo w and rapid genotype and phenotype. The kidney p-aminobenzoic acid/Nat2-ace tylating activity of CD-1 female mice showed a 2.5-fold increase at 80 days of age compared with day 1, whereas males showed a 4.3-fold increase at 25 days and a 5.8-fold increase at 80 days. Immunoblot analysis revealed a 2- fold increase in male kidney Nat immunoreactive protein at 80 days of age, whereas no significant differences were detected in female mice. Likewise, the Nat2 mRNA levels determined by ribonuclease protection assay showed an increase in transcript levels in kidney of male mice during postnatal devel opment, whereas they remained unchanged in females. Gender-associated diffe rences of Nat2 activity, protein, and transcript levels were absent in live r. These observations suggest that the increase in Nat2 enzymatic activity in kidney is accomplished by an increase in transcript. We propose that the observed increase in Nat2 transcript expression in male mice may be a resu lt of androgen regulation during development.