Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.

ABSTRACT:

Background

Folic acid supplementation prevents the occurrence and recurrence of neural tube defects (NTDs), but the causal metabolic pathways underlying folic acid-responsive NTDs have not been established. Serine hydroxymethyltransferase (SHMT1) partitions folate-derived one-carbon units to thymidylate biosynthesis at the expense of cellular methylation, and therefore SHMT1-deficient mice are a model to investigate the metabolic origin of folate-associated pathologies.

Objectives

We examined whether genetic disruption of the Shmt1 gene in mice induces NTDs in response to maternal folate and choline deficiency and whether a corresponding disruption in de novo thymidylate biosynthesis underlies NTD pathogenesis.

Design

Shmt1 wild-type, Shmt1(+/-), and Shmt1(-/-) mice f

SUBMITTER: Beaudin AE 

PROVIDER: S-EPMC3057548 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature