Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 2, 2000
Publication Date: July 20, 2001
Citation: Vallet, J.L., Smith, T.P., Sonstegard, T.S., Heaton, M.P., Fahrenkrug, S.C. 2001. Structure of the genes for porcine endometrial secreted and membrane folate binding proteins. Domestic Animal Endocrinology. 21(1):55-72. Interpretive Summary: The developing pig fetus requires the vitamin, folate, for red blood cell synthesis. Folates are delivered to the pig fetus bound to two different folate binding proteins, a soluble form that is free in the intrauterine environment, and a receptor form that is attached to uterine and placental cells. The soluble form increases in the intrauterine lumen during early pregnancy, and very little is known about the control of the receptor form In this experiment, we isolated and sequenced the genes for the soluble and receptor forms of folate binding proteins, to obtain clues to the control of each of these proteins during pregnancy in swine. Results indicated that the gene sequences for the soluble and receptor forms were similar to human genes performing similar functions, and in fact shared sequence homology with the upstream controlling regions of the corresponding human genes. We also found that sequences within introns 3 and 4 of the soluble and receptor forms of porcine folate binding protein genes were highly similar suggesting that sequences within these introns may control gene expression. These results provide clues to the control of genes involved in folate metabolism during pregnancy, and may lead to increased folate delivery, improved red blood cell synthesis by the developing pig fetus, and improved fetal survival during pregnancy in swine.
Technical Abstract: The endometrium of the pig produces two types of folate binding proteins (FBP) which, based on their sequences, are likely to be membrane (m) and secreted (s) forms. A clone containing both a gene coding for the sFBP cDNA and a gene coding for the mFBP was isolated from a yeast artificial chromosome (YAC) library. Each gene was subcloned and sequenced. The gene for sFBP spanned 4.4 kbp and included 5 exons. The mFBP gene spanned 7.0 kbp and also contained 5 exons. Structures of the genes were very similar for the last three exons, and this similarity was shared with other known FBP/folate receptor (FR) gene sequences. Unexpectedly, portions of introns 3 and 4 of both genes were highly homologous, suggesting the possibility that sequences within these introns served some as yet unknown function. In contrast, the structures of the 5' exons differed between the two genes and other known FBP/FR genes. Comparison of putative promoter regions for the two genes with promoter regions for human FBP/FR genes revealed significan sequence homology between sFBP and human gamma FBP and between mFBP and human alpha FR. These regions of homology may play a role in control of transcription of each gene.