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Gene Review

Folr1  -  folate receptor 1 (adult)

Mus musculus

Synonyms: FBP1, FR-alpha, Fbp1, Folate receptor 1, Folate receptor alpha, ...
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Disease relevance of Folr1

  • In conclusion, Folbp1 and RFC1 genetically modified mice exhibit distinct changes in colonocyte phenotype and therefore have utility as models to examine the role of folate homeostasis in colon cancer development [1].
  • Embryonic lethality and neural tube defect (NTD) frequency in Folbp1 mice was dose-dependent and differed from the RFC mice; however, no genotype-related differences were observed [2].
  • It is concluded that genetic modifications at the Folbp1 and RFC loci confers no particular sensitivity to arsenic toxicity compared to wild-type controls, thus disproving the working hypothesis that decreased methylating capacity of the genetically modified mice would put them at increased risk for arsenic-induced reproductive toxicity [2].
  • Distinguishing between folate receptor-alpha-mediated transport and reduced folate carrier-mediated transport in L1210 leukemia cells [3].
  • The expression of a membrane-associated folate receptor (FR) was elevated in spleen samples from patients with chronic (CML) and acute (AML) myelogenous leukemias compared with normal spleen [4].

Psychiatry related information on Folr1


High impact information on Folr1


Chemical compound and disease context of Folr1


Biological context of Folr1

  • Microarray analysis of colonic mucosa showed distinct changes in gene expression specific to Folbp1 or RFC1 ablation [1].
  • Furthermore, additional amino acid sequence divergence at one or more positions downstream of residue 92 in FR-alpha is also an essential determinant of the unique functional characteristics of this receptor isoform [12].
  • Reciprocal substitution in FR-beta with peptide 1-92 of FR-alpha resulted in poor expression of a [3H]folic acid binding protein [12].
  • As the chromosomal locations of Folbp1 murine and Folbp2 genes were previously unknown, we utilized the same approach and mapped both genes to a region of mouse chromosome 7 that is syntenic to the human FR loci on chromosome 11q13 [13].
  • We now report on the transfection of MTXrA with a cDNA encoding the murine homolog of the human folate receptor isoform of KB cells to produce MTXrA-TF1, which constitutively expresses high levels of FR-alpha [3].

Anatomical context of Folr1


Associations of Folr1 with chemical compounds

  • Using an oligonucleotide probe complementary to the human FBP, we have cloned and sequenced two murine FBP cDNAs isolated from a library constructed using a L1210 subline adapted for growth on low levels of 5-formyltetrahydrofolate [14].
  • The highly sensitive SWV strain demonstrated a significant reduction in the expression of the folate binding protein (FBP-1) following the teratogenic insult at gestational day 8:18, while the more resistant LM/Bc embryos were up-regulating this gene in response to valproic acid treatment [18].
  • The MTXrA cells provide an example of a line selected for primary resistance to methotrexate that also exhibits concomitant increased expression of a folate-binding protein [19].
  • FR-alpha expressed at sufficient levels can mediate influx of MTX and folates into cells at rates comparable to the reduced folate carrier and hence has pharmacologic and physiologic importance [3].
  • Probenecid and sulfobromophthalein inhibit methotrexate influx in both L1210 and MTXrA-TF1 cell lines; however, inhibition in MTXrA-TF1 could be accounted for on the basis of inhibition of methotrexate binding to FR-alpha [3].

Other interactions of Folr1


Analytical, diagnostic and therapeutic context of Folr1


  1. Folate transport gene inactivation in mice increases sensitivity to colon carcinogenesis. Ma, D.W., Finnell, R.H., Davidson, L.A., Callaway, E.S., Spiegelstein, O., Piedrahita, J.A., Salbaum, J.M., Kappen, C., Weeks, B.R., James, J., Bozinov, D., Lupton, J.R., Chapkin, R.S. Cancer Res. (2005) [Pubmed]
  2. Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies. Spiegelstein, O., Gould, A., Wlodarczyk, B., Tsie, M., Lu, X., Le, C., Troen, A., Selhub, J., Piedrahita, J.A., Salbaum, J.M., Kappen, C., Melnyk, S., James, J., Finnell, R.H. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
  3. Distinguishing between folate receptor-alpha-mediated transport and reduced folate carrier-mediated transport in L1210 leukemia cells. Spinella, M.J., Brigle, K.E., Sierra, E.E., Goldman, I.D. J. Biol. Chem. (1995) [Pubmed]
  4. Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Shen, F., Ross, J.F., Wang, X., Ratnam, M. Biochemistry (1994) [Pubmed]
  5. Embryonic development of folate binding protein-1 (Folbp1) knockout mice: Effects of the chemical form, dose, and timing of maternal folate supplementation. Spiegelstein, O., Mitchell, L.E., Merriweather, M.Y., Wicker, N.J., Zhang, Q., Lammer, E.J., Finnell, R.H. Dev. Dyn. (2004) [Pubmed]
  6. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Piedrahita, J.A., Oetama, B., Bennett, G.D., van Waes, J., Kamen, B.A., Richardson, J., Lacey, S.W., Anderson, R.G., Finnell, R.H. Nat. Genet. (1999) [Pubmed]
  7. Transduction of folate receptor cDNA into cervical carcinoma cells using recombinant adeno-associated virions delays cell proliferation in vitro and in vivo. Sun, X.L., Murphy, B.R., Li, Q.J., Gullapalli, S., Mackins, J., Jayaram, H.N., Srivastava, A., Antony, A.C. J. Clin. Invest. (1995) [Pubmed]
  8. Comparison of methotrexate polyglutamylation in L1210 leukemia cells when influx is mediated by the reduced folate carrier or the folate receptor. Lack of evidence for influx route-specific effects. Spinella, M.J., Brigle, K.E., Freemantle, S.J., Sierra, E.E., Goldman, I.D. Biochem. Pharmacol. (1996) [Pubmed]
  9. Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta-targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid. Pan, X.Q., Zheng, X., Shi, G., Wang, H., Ratnam, M., Lee, R.J. Blood (2002) [Pubmed]
  10. Role of membrane folate-binding protein in the cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cell lines in vitro. Sen, S., Erba, E., D'Incalci, M., Bottero, F., Canevari, S., Tomassetti, A. Br. J. Cancer (1996) [Pubmed]
  11. In vivo antitumor activity of folate receptor-targeted liposomal daunorubicin in a murine leukemia model. Pan, X.Q., Lee, R.J. Anticancer Res. (2005) [Pubmed]
  12. Identification of amino acid residues that determine the differential ligand specificities of folate receptors alpha and beta. Shen, F., Zheng, X., Wang, J., Ratnam, M. Biochemistry (1997) [Pubmed]
  13. Identification of two putative novel folate receptor genes in humans and mouse. Spiegelstein, O., Eudy, J.D., Finnell, R.H. Gene (2000) [Pubmed]
  14. Characterization of two cDNAs encoding folate-binding proteins from L1210 murine leukemia cells. Increased expression associated with a genomic rearrangement. Brigle, K.E., Westin, E.H., Houghton, M.T., Goldman, I.D. J. Biol. Chem. (1991) [Pubmed]
  15. Renal tubular reabsorption of folate mediated by folate binding protein 1. Birn, H., Spiegelstein, O., Christensen, E.I., Finnell, R.H. J. Am. Soc. Nephrol. (2005) [Pubmed]
  16. Structure and regulation of the murine reduced folate carrier gene: identification of four noncoding exons and promoters and regulation by dietary folates. Liu, M., Ge, Y., Cabelof, D.C., Aboukameel, A., Heydari, A.R., Mohammad, R., Matherly, L.H. J. Biol. Chem. (2005) [Pubmed]
  17. Expression of folate receptor alpha in the mammalian retinol pigmented epithelium and retina. Smith, S.B., Kekuda, R., Gu, X., Chancy, C., Conway, S.J., Ganapathy, V. Invest. Ophthalmol. Vis. Sci. (1999) [Pubmed]
  18. Strain-dependent alterations in the expression of folate pathway genes following teratogenic exposure to valproic acid in a mouse model. Finnell, R.H., Wlodarczyk, B.C., Craig, J.C., Piedrahita, J.A., Bennett, G.D. Am. J. Med. Genet. (1997) [Pubmed]
  19. Increased expression and genomic organization of a folate-binding protein homologous to the human placental isoform in L1210 murine leukemia cell lines with a defective reduced folate carrier. Brigle, K.E., Seither, R.L., Westin, E.H., Goldman, I.D. J. Biol. Chem. (1994) [Pubmed]
  20. Role of Folbp1 in the regional regulation of apoptosis and cell proliferation in the developing neural tube and craniofacies. Tang, L.S., Santillano, D.R., Wlodarczyk, B.J., Miranda, R.C., Finnell, R.H. American journal of medical genetics. Part C, Seminars in medical genetics. (2005) [Pubmed]
  21. Insertion of an intracisternal A particle within the 5'-regulatory region of a gene encoding folate-binding protein in L1210 leukemia cells in response to low folate selection. Association with increased protein expression. Brigle, K.E., Westin, E.H., Houghton, M.T., Goldman, I.D. J. Biol. Chem. (1992) [Pubmed]
  22. Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors. Reddy, J.A., Abburi, C., Hofland, H., Howard, S.J., Vlahov, I., Wils, P., Leamon, C.P. Gene Ther. (2002) [Pubmed]
  23. A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida. Zhu, H., Yang, W., Lu, W., Zhang, J., Shaw, G.M., Lammer, E.J., Finnell, R.H. Mol. Genet. Metab. (2006) [Pubmed]
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