Changing of N-linked glycosylation in β1,4-GalT1 site-specific mutant mouse

Session: 
S4.1 Glycosyl transferases
Code: 
OL4.1.3
Location (hall): 
Glucose
Start/end time: 
Tuesday, July 2, 2019 - 12:15 to 12:30
Ran
Cao

Ran Cao1, Josef Voglmeir1, Li Liu1

1Nanjing Agricultural University, Nanjing, China

β1,4-GalT1 is type II membrane-bound glycoprotein transferring galactose to acceptor sugars. This enzyme catalyzes the synthesis of lactose or transfers galactose to the terminal GlcNAc of complex-type N-glycans. Previous studies found that β1,4-GalT1 knock-out mouse showed semi-lethality after birth. We obtained a β1,4-GalT1 site-specific mutant mouse modelusing CRISPR/Cas9 in which tyrosine (Y286) were substituted by leucine (L286). This mutation makes β1,4-GalT1 an N-acetylgalactosaminetransferase instead of galactosyltransferase. No lethal deficiency was observed in both heterozygote (+/-) mice and homozygous (-/-) mice. However, homozygous (-/-) mice were unable to give birth and lactation. The further N-glycan profiling showed that homozygous (-/-) mouse serum have no sialylated N-glycans while heterozygote(+/-) mouse showed the similar pattern of N-glycosylation in serum compared with wild-type mouse. The results indicated that the functional changing of galactosyltransferase in homozygous (-/-) mouse leads to a serious interfere of N-glycosylation and might cause the physiological defect of lactation and pregnancy.

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