ABSTRACT
I. Introduction .................................................................................................. 156 A. The Neural Crest and Metabolic Demand for Folate ............................... 157 B. Biochemical Pathways ............................................................................. 157 C. Hcy Metabolism ....................................................................................... 159
II. Role of Folate in Susceptibility to Birth Defects .......................................... 159 A. Folate De ciency ..................................................................................... 159 B. Folate Agonists ........................................................................................ 160 C. Antibodies against Folate Receptors ....................................................... 161 D. Gene Polymorphisms ............................................................................... 161
III. Intracellular Folate Transport ....................................................................... 163 IV. Murine Models of Compromised Folate Uptake and Biotransformation:
Folr1, Folr2, Rfc1, Pcft, and Mthfr ............................................................... 163 A. Folr1 ......................................................................................................... 163 B. Folr2 ......................................................................................................... 168 C. Rfc1/Slc19A1 ............................................................................................ 168 D. Pcft/Hcp1 ................................................................................................. 169 E. Mthfr ........................................................................................................ 169
V. Summary ...................................................................................................... 170 Glossary ........................................................................................................ 170 Acknowledgments ......................................................................................... 171 References ..................................................................................................... 171
Birth defects are a global problem that affect approximately 6% of all births [1]. In the United States, birth defects are the leading cause of hospitalizations [2], medical expenditures [3], and death in the rst year of life [4]. Worldwide, at least 3.3 million children under the age of 5 years die each year because of a serious birth defect [1]. Indeed, birth defects are one, if not the leading, health care concern for the youngest members of our societies.
