Rescue of Embryonic Lethality in Reduced Folate Carrier-deficient Mice by Maternal Folic Acid Supplementation Reveals Early Neonatal Failure of Hematopoietic Organs

Rongbao Zhao, Robert G. Russell, Yanhua Wang, Laibin Liu, Feng Gao, Burkhard Kneitz, Winfried Edelmann, I. David Goldman

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The reduced folate carrier (RFC1) is an important route by which the major blood folate, 5-methyltetrahydrofolate, is transported into mammalian cells. In this study we determined the consequences of inactivation of RFC1 in mice by homologous recombination. While RFC1-/- embryos died in utero before embryonic day 9.5 (E9.5), near-normal development could be sustained in RFC1-/- embryos examined at E18.5 by supplementation of pregnant RFC1+/- dams with 1-mg daily subcutaneous doses of folic acid. About 10% of these animals went on to live birth but died within 12 days. These RFC1-/- mice showed a marked absence of erythropoiesis in bone marrow, spleen, and liver along with lymphoid depletion in the splenic white pulp and thymus. In addition, there was some impairment of renal and seminiferous tubule development. These data indicate that in the absence of RFC1 function, neonatal animals die due to failure of hematopoietic organs.

Original languageEnglish (US)
Pages (from-to)10224-10228
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number13
StatePublished - Mar 30 2001

Fingerprint

Reduced Folate Carrier Protein
Folic Acid
Animals
Embryonic Structures
Mothers
Newborn Animals
Thymus
Seminiferous Tubules
Erythropoiesis
Homologous Recombination
Live Birth
Liver
Thymus Gland
Dams
Pulp
Bone
Blood
Spleen
Bone Marrow
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{cee1eb8350914d52a950751ada25dce0,
title = "Rescue of Embryonic Lethality in Reduced Folate Carrier-deficient Mice by Maternal Folic Acid Supplementation Reveals Early Neonatal Failure of Hematopoietic Organs",
abstract = "The reduced folate carrier (RFC1) is an important route by which the major blood folate, 5-methyltetrahydrofolate, is transported into mammalian cells. In this study we determined the consequences of inactivation of RFC1 in mice by homologous recombination. While RFC1-/- embryos died in utero before embryonic day 9.5 (E9.5), near-normal development could be sustained in RFC1-/- embryos examined at E18.5 by supplementation of pregnant RFC1+/- dams with 1-mg daily subcutaneous doses of folic acid. About 10{\%} of these animals went on to live birth but died within 12 days. These RFC1-/- mice showed a marked absence of erythropoiesis in bone marrow, spleen, and liver along with lymphoid depletion in the splenic white pulp and thymus. In addition, there was some impairment of renal and seminiferous tubule development. These data indicate that in the absence of RFC1 function, neonatal animals die due to failure of hematopoietic organs.",
author = "Rongbao Zhao and Russell, {Robert G.} and Yanhua Wang and Laibin Liu and Feng Gao and Burkhard Kneitz and Winfried Edelmann and Goldman, {I. David}",
year = "2001",
month = "3",
day = "30",
language = "English (US)",
volume = "276",
pages = "10224--10228",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "13",

}

TY - JOUR

T1 - Rescue of Embryonic Lethality in Reduced Folate Carrier-deficient Mice by Maternal Folic Acid Supplementation Reveals Early Neonatal Failure of Hematopoietic Organs

AU - Zhao, Rongbao

AU - Russell, Robert G.

AU - Wang, Yanhua

AU - Liu, Laibin

AU - Gao, Feng

AU - Kneitz, Burkhard

AU - Edelmann, Winfried

AU - Goldman, I. David

PY - 2001/3/30

Y1 - 2001/3/30

N2 - The reduced folate carrier (RFC1) is an important route by which the major blood folate, 5-methyltetrahydrofolate, is transported into mammalian cells. In this study we determined the consequences of inactivation of RFC1 in mice by homologous recombination. While RFC1-/- embryos died in utero before embryonic day 9.5 (E9.5), near-normal development could be sustained in RFC1-/- embryos examined at E18.5 by supplementation of pregnant RFC1+/- dams with 1-mg daily subcutaneous doses of folic acid. About 10% of these animals went on to live birth but died within 12 days. These RFC1-/- mice showed a marked absence of erythropoiesis in bone marrow, spleen, and liver along with lymphoid depletion in the splenic white pulp and thymus. In addition, there was some impairment of renal and seminiferous tubule development. These data indicate that in the absence of RFC1 function, neonatal animals die due to failure of hematopoietic organs.

AB - The reduced folate carrier (RFC1) is an important route by which the major blood folate, 5-methyltetrahydrofolate, is transported into mammalian cells. In this study we determined the consequences of inactivation of RFC1 in mice by homologous recombination. While RFC1-/- embryos died in utero before embryonic day 9.5 (E9.5), near-normal development could be sustained in RFC1-/- embryos examined at E18.5 by supplementation of pregnant RFC1+/- dams with 1-mg daily subcutaneous doses of folic acid. About 10% of these animals went on to live birth but died within 12 days. These RFC1-/- mice showed a marked absence of erythropoiesis in bone marrow, spleen, and liver along with lymphoid depletion in the splenic white pulp and thymus. In addition, there was some impairment of renal and seminiferous tubule development. These data indicate that in the absence of RFC1 function, neonatal animals die due to failure of hematopoietic organs.

UR - http://www.scopus.com/inward/record.url?scp=0035971190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035971190&partnerID=8YFLogxK

M3 - Article

VL - 276

SP - 10224

EP - 10228

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -