Folate-regulated changes in gene expression in the anterior neural tube of folate binding protein-1 (Folbp1)-deficient murine embryos.
Inactivation of the murine folate binding protein-1 (Folbp1) has been shown to play a vital role in embryonic development. Nullizygous embryos (Folbp1-/-) have significant malformations of the neural tube, craniofacies, and conotruncus, and invariably die in utero by gestational day (E) 10. Administration of 25 mg x kg(-1) x day(-1) folinic acid to dams prior to and throughout gestation rescues the majority of embryos from premature death; however, a portion of surviving embryos develops neural tube defects. Using antisense RNA amplification and cDNA microarrays, we examined the expression of approximately 5700 genes in the anterior neural tube of gestational day 9 Folbp1-/- embryos that were supplemented with folinic acid. Genes that appear to be folate regulated include transcription factors, G-proteins, growth factors, methyltransferases, and those that are related to cell proliferation. The potential impact of such changes during neural tube closure is considered in light of the phenotype of Folbp1-/- embryos.
Spiegelstein
Ofer
O
Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030, USA.
Cabrera
Robert M
RM
Bozinov
Daniel
D
Wlodarczyk
Bogdan
B
Finnell
Richard H
RH
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D009420:Nervous System / Q000196:embryology*; D009693:Nucleic Acid Hybridization; D011956:Receptors, Cell Surface / Q000235:genetics*
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid