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Aberration of Serum and Tissue N-Glycans in Mouse β1,4-GalT1 Y286L Mutant Variants.

Authors
  • Cao, Ran1
  • Zhang, Tian-Chan1
  • Chen, Ya-Ran1
  • Cao, Cui1
  • Chen, Huan1
  • Huang, Yi-Fan2
  • Fujita, Morihisa2
  • Liu, Li3
  • Voglmeir, Josef4
  • 1 Glycomics and Glycan Bioengineering Research Center (GGBRC), College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China. , (China)
  • 2 Key Laboratory of Carbohydrate Chemistry and Biotechnology, School of Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China. , (China)
  • 3 Glycomics and Glycan Bioengineering Research Center (GGBRC), College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China. [email protected] , (China)
  • 4 Glycomics and Glycan Bioengineering Research Center (GGBRC), College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China. [email protected] , (China)
Type
Published Article
Journal
Glycoconjugate Journal
Publisher
Springer-Verlag
Publication Date
Dec 01, 2020
Volume
37
Issue
6
Pages
767–775
Identifiers
DOI: 10.1007/s10719-020-09946-8
PMID: 32926333
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

β1,4-GalT1 is a type II membrane glycosyltransferase. It catalyzes the production of lactose in the lactating mammary gland and is supposedly also involved in the galactosylation of terminal GlcNAc of complex-type N-glycans. In-vitro studies of the bovine β4Gal-T1 homolog showed that replacing a single residue of tyrosine with leucine at position 289 alters the donor substrate specificity from UDP-Gal to UDP-N-acetyl-galactosamine (UDP-GalNAc). The effect of this peculiar change in β1,4GalT1 specificity was investigated in-vivo, by generating biallelic Tyr286Leu β1,4GalT1 mice using CRISPR/Cas9 and crossbreeding. Mice bearing this mutation showed no appreciable defects when compared to wild-type mice, with the exception of biallelic female B4GALT1 mutant mice, which were unable to produce milk. The detailed comparison of wild-type and mutant mice derived from liver, kidney, spleen, and intestinal tissues showed only small differences in their N-glycan pattern. Comparable N-glycosylation was also observed in HEK 293 wild-type and knock-out B4GALT1 cells. Remarkably and in contrast to the other analyzed tissue samples, sialylation and galactosylation of serum N-glycans of biallelic Tyr286Leu GalT1 mice almost disappeared completely. These results suggest that β1,4GalT1 plays a special role in the synthesis of serum N-glycans. The herein described Tyr286Leu β1,4GalT1 mutant mouse model may, therefore, prove useful in the investigation of the mechanism which regulates tissue-dependent galactosylation.

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