Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates

Ella Ioffe, Pamela Stanley

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330 Citations (Scopus)

Abstract

Eukaryotic cells require N-linked carbohydrates for survival. However, the biosynthetic intermediate Man5GlcNAc2Asn, in place of mature N-linked structures, allows glycoprotein synthesis and somatic cell growth to proceed normally. To determine whether the same would be true in a complex biological situation, the gene Mgat-1 was disrupted by homologous recombination in embryonic stem cells and transmitted to the germ line. The Mgat-1 gene encodes N-acetylglucosaminyltransferase I [GlcNAc-TI; α-1,3-mannosyl-glycoprotein β-1,2-JV-acetylglucosaminyltransferase; UDP-N-acetyl-D-glucosamine:glycoprotein (N-acetyl-D-glucosamine to α-D-mannosyl-1,3-(R1)-β-D-mannosyl-R2) β-1,2-N-acetyl-D-glucosaminyltransferase, EC 2.4.1.101], the transferase that initiates synthesis of hybrid and complex N-linked carbohydrates from Man5GlcNAc2Asn. Mice lacking GlcNAc-TI activity did not survive to term. Biochemical and morphological analyses of embryos from 8.5 to 13.5 days of gestation showed that Mgat-1-/- embryos are developmentally retarded, most noticeably in neural tissue, and die between 9.5 and 10.5 days of development.

Original languageEnglish (US)
Pages (from-to)728-732
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number2
StatePublished - Jan 18 1994

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Glycoproteins
Acetylglucosamine
Carbohydrates
Pregnancy
Embryonic Structures
Uridine Diphosphate
Homologous Recombination
Eukaryotic Cells
Embryonic Stem Cells
Transferases
Germ Cells
Genes
Growth
alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase I

Keywords

  • Glycobiology
  • Glycosyltransferase gene
  • Homologous recombination
  • Mouse development

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates",
abstract = "Eukaryotic cells require N-linked carbohydrates for survival. However, the biosynthetic intermediate Man5GlcNAc2Asn, in place of mature N-linked structures, allows glycoprotein synthesis and somatic cell growth to proceed normally. To determine whether the same would be true in a complex biological situation, the gene Mgat-1 was disrupted by homologous recombination in embryonic stem cells and transmitted to the germ line. The Mgat-1 gene encodes N-acetylglucosaminyltransferase I [GlcNAc-TI; α-1,3-mannosyl-glycoprotein β-1,2-JV-acetylglucosaminyltransferase; UDP-N-acetyl-D-glucosamine:glycoprotein (N-acetyl-D-glucosamine to α-D-mannosyl-1,3-(R1)-β-D-mannosyl-R2) β-1,2-N-acetyl-D-glucosaminyltransferase, EC 2.4.1.101], the transferase that initiates synthesis of hybrid and complex N-linked carbohydrates from Man5GlcNAc2Asn. Mice lacking GlcNAc-TI activity did not survive to term. Biochemical and morphological analyses of embryos from 8.5 to 13.5 days of gestation showed that Mgat-1-/- embryos are developmentally retarded, most noticeably in neural tissue, and die between 9.5 and 10.5 days of development.",
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T1 - Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates

AU - Ioffe, Ella

AU - Stanley, Pamela

PY - 1994/1/18

Y1 - 1994/1/18

N2 - Eukaryotic cells require N-linked carbohydrates for survival. However, the biosynthetic intermediate Man5GlcNAc2Asn, in place of mature N-linked structures, allows glycoprotein synthesis and somatic cell growth to proceed normally. To determine whether the same would be true in a complex biological situation, the gene Mgat-1 was disrupted by homologous recombination in embryonic stem cells and transmitted to the germ line. The Mgat-1 gene encodes N-acetylglucosaminyltransferase I [GlcNAc-TI; α-1,3-mannosyl-glycoprotein β-1,2-JV-acetylglucosaminyltransferase; UDP-N-acetyl-D-glucosamine:glycoprotein (N-acetyl-D-glucosamine to α-D-mannosyl-1,3-(R1)-β-D-mannosyl-R2) β-1,2-N-acetyl-D-glucosaminyltransferase, EC 2.4.1.101], the transferase that initiates synthesis of hybrid and complex N-linked carbohydrates from Man5GlcNAc2Asn. Mice lacking GlcNAc-TI activity did not survive to term. Biochemical and morphological analyses of embryos from 8.5 to 13.5 days of gestation showed that Mgat-1-/- embryos are developmentally retarded, most noticeably in neural tissue, and die between 9.5 and 10.5 days of development.

AB - Eukaryotic cells require N-linked carbohydrates for survival. However, the biosynthetic intermediate Man5GlcNAc2Asn, in place of mature N-linked structures, allows glycoprotein synthesis and somatic cell growth to proceed normally. To determine whether the same would be true in a complex biological situation, the gene Mgat-1 was disrupted by homologous recombination in embryonic stem cells and transmitted to the germ line. The Mgat-1 gene encodes N-acetylglucosaminyltransferase I [GlcNAc-TI; α-1,3-mannosyl-glycoprotein β-1,2-JV-acetylglucosaminyltransferase; UDP-N-acetyl-D-glucosamine:glycoprotein (N-acetyl-D-glucosamine to α-D-mannosyl-1,3-(R1)-β-D-mannosyl-R2) β-1,2-N-acetyl-D-glucosaminyltransferase, EC 2.4.1.101], the transferase that initiates synthesis of hybrid and complex N-linked carbohydrates from Man5GlcNAc2Asn. Mice lacking GlcNAc-TI activity did not survive to term. Biochemical and morphological analyses of embryos from 8.5 to 13.5 days of gestation showed that Mgat-1-/- embryos are developmentally retarded, most noticeably in neural tissue, and die between 9.5 and 10.5 days of development.

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KW - Glycosyltransferase gene

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