Disease relevance of Mgat1

• A tissue culture model which displays an increase in expression of the approximately 3.3 kb Mgat-1 mRNA transcript during differentiation to neuronal cells has been developed in P19 embryonal carcinoma (EC) cells [1].

High impact information on Mgat1

• Complex N-linked oligosaccharide biosynthesis is initiated in the Golgi apparatus by the action of Mgat-1-encoded UDP-N-acetylglucosamine:alpha-3-D- mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI) [2].
• The Mgat1 gene encodes N-acetylglucosaminyltransferase I (Glc-NAc-TI; EC 2.4.1.101), the transferase that initiates the synthesis of complex N-glycans [3].
• To circumvent this embryonic lethality and to uncover tissue-specific functions for complex N-glycans, WW6 embryonic stem cells with inactivated Mgat1 alleles were tracked in chimeric embryos [3].
• This deficiency was corrected by transfection of a Mgat1 transgene [3].
• Furthermore, examination of lung bud in E9.5 Mgat1-/- mutant embryos showed complete absence of an organized epithelial cell layer in the bronchus [3].

Biological context of Mgat1

• Nevertheless, a requirement for hybrid and complex N-glycan branching exists in embryonic development and postnatal function among mice and humans inheriting defective Mgat1 or Mgat2 alleles [4].
• Loss of Mgat1 resulted in a unique pattern of neuronal glycoprotein deficiency concurrent with caspase 3 activation and apoptosis [4].
• We have isolated the mouse gene encoding GlcNAc-TI (Mgat-1) from a genomic DNA library [5].
• Mgat-1 was mapped to mouse Chromosome 11, closely linked to the gene encoding interleukin-3 by the analysis of multilocus interspecies backcrosses [5].
• The combined data suggest that 5' exons in the Mgat-1 gene are differentially utilized by tissue-specific promoters and that transcription factor(s) which specify production of the approximately 3.3 kb Mgat-1 mRNA are induced by retinoic acid treatment of P19 EC cells [1].

Anatomical context of Mgat1

• 5. Complex N-glycans were not observed in E7.5-E9.5 Mgat1-null embryos with the notable exception of vesicular structures within cells of the visceral extra-embryonic endoderm, perhaps reflecting the ability of these cells to take up and transport maternally derived glycoproteins [6].
• Interestingly, heterozygous Mgat1+/- WW6 cells were also deficient in populating the layer of bronchial epithelium [3].
• The administration of kappa-opioid receptor antagonists, nor-binaltorphimine (norBNI) and 5'-guanidinonaltrindole (GNTI) enhanced allodynia in rats and mice after sciatic nerve ligation [7].

Associations of Mgat1 with chemical compounds

• Complex asparagine-linked oligosaccharides in Mgat1-null embryos [6].
• To investigate the developmental role of complex N-linked oligosaccharides, we previously inactivated the mouse Mgat1 gene which encodes UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI) [6].
• The potentiation of allodynia after the administration of norBNI or GNTI was inhibited by earlier administration of DYN A/S or by ketamine [7].

Analytical, diagnostic and therapeutic context of Mgat1

• We now show, by in situ hybridization of horizontal sections of adult mouse brain, that Mgat-1 RNA levels vary markedly in different brain cell types with the greatest expression being in neuronal cells [1].
• This probe hybridized uniquely to the approximately 3.3 kb Mgat-1 mRNA and Southern blot analysis showed that the new sequence is physically linked to the Mgat-1 gene [1].

References