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Updated: Jun 18, 2026
03:19
Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes
Published on: June 28, 2024
N-acetyltransferase 2 activity and folate levels.
Wen Cao1, Diana Strnatka, Charlene A McQueen
1Department of Pediatrics, University of Arizona, Tucson, AZ 85724-5073, USA.
Life Sciences
|November 26, 2009
Summary
Increased N-acetyltransferase (NAT) activity, specifically human NAT1, was investigated for toxic effects and folate level impacts in mice. Results indicate that higher NAT activity correlates with decreased folate levels, suggesting potential folate catabolism.
Area of Science:
- Biochemistry
- Toxicology
- Genetics
Background:
- Previous research indicated limitations in achieving high exogenous N-acetyltransferase (NAT) levels in transgenic mice.
- Understanding the developmental toxicity and impact on folate metabolism of increased NAT activity is crucial.
Purpose of the Study:
- To investigate the potential toxic effects of elevated N-acetyltransferase (NAT) activity during development.
- To determine the influence of increased NAT activity on folate levels in a mouse model.
Main Methods:
- Utilized a human NAT1 tet-inducible construct in transgenic mice, with expression controlled by doxycycline.
- Generated transgenic mouse lines by injecting human NAT1 cDNA into oocytes and crossing with a 'tet(on)' mouse line.
- Measured red blood cell folate levels in inbred mouse strains.
Main Results:
- Achieved only low levels of human NAT1 expression in the kidney, irrespective of doxycycline administration method (gavage or drinking water).
- Observed an inverse correlation between folate levels and Nat2 enzyme activity.
- Demonstrated that increased NAT1 activity leads to decreased folate levels in at least one tissue.
Conclusions:
- The detrimental effect of human NAT1 expression, combined with endogenous mouse Nat2, may stem from enhanced folate catabolism.
- Findings suggest a potential mechanism linking NAT activity to folate homeostasis disruption.
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