The use of mouse models to elucidate the genetic and environmental components of neural tube defects

Abstract

Neural tub defects (NTDs) rank among the most common phics. congenital anomalies affecting human infants worldwide. Unfortunately, the: etiology is poorly understood accuse the genetic and environmental components contributing to their expression are extremely complex. Inbred mouse strains are highly regarded as animal models for studying the etiology of NTDS because their genetics are so well characterized and there is a high degree of homology between human and murine genomes. Furthermore, it is thought that murine neuruation follows a pattern very similar to that of humans. Two of the more popular murine models for the study of NTDS are the Splotch and curly-tail mutant mice. We used curly-tail mice to examine the genetic factors contributing to spinal ' NTDS. The nGNA levels of genes implicated in the curly-tail phenotype, as well as other candidate genes for NTDS, were quantified over five timepoints during neurulation by RT/aRNA amplification. Our observations confirm a role for [] and [] CT spinal NTDS and identify a new genetic factor contributing to these defects, TGF-R. To otter clarify the impact of environmental factors on NTDS, Splotch mice were used to examine the role of supplemental folate on the induced NTDS. Two forms of notate, folic acid and folinic acid, were examined. Folic acid or folinic acid administered alone did not ameliorate the incidence of spontaneous NTDS in Splotch mice. Folic acid protected against arsenic-induced NTDS by selective resolution of affected conceptuses, while folic acid induced lethality in arsenic treated animals.