Normal development and fertility of Fut1, Fut2, and Sec1 triple knockout mice

Abstract

Abbreviations:Fut1, a-2 fucosyltransferase I; Fut2, a-2 fucosyltransferase II; Sec1, a-2 fucosyltransferase III; Blood group H, Fuc a2 Gal b; Blood group A, GalNAc a3 Fuc a2 Gal b; Blood group B, Gal a3 Fuc a2 Gal b; CFG, consortium of functional glycomics; Lewis y, Fuc a2 Gal b4 (a3) GlcNAc b; Type I H, Fuc a2 Gal b3 GlcNAc b; Type II H, Fuc a2 Gal b4 GlcNAc b; Type III H, Fuc a2 Gal b3 GalNAc a;Type IV H, Fuc a2 Gal b3 GalNAc b;Type VI H, Fuc a2 Gal b4 Glc b AbstractThe fucose alpha(1,2) galactose structure (H antigen) is synthesized by a1,2 fucosyltransferases Fut1, Fut2 and Sec1. H antigen has been reported to be involved in cancer progression, neurite migration, synaptic plasticity, host-microbe interaction, blastocyst implantation, and the maintenance of gut microbiome. Genetic depletion of Fut1 or Fut2 only cause defects of alpha1,2 fucosylation in limited tissues because of enzyme redundancy. In this study, we generated mice with deficiencies in Fut1, Fut2, and Sec1 genes to deplete H antigen through BAC Engineering for the generation of ES Cell-Targeting construct. The homogenous triple knockout mice showed no significant decrease of viability or development. Mass spectrometry and Western blot analysis confirmed the absence of H blood group antigen in multiple organs. These results indicate normal development and fertility of mice devoid of blood group H. The fine pathophysiological alterations in these mice remain to be carefully studied, and they may serve as valuable tools to study gut microbiome and host-microbe interactions.

In situ spatial glycomic imaging of mouse and human Alzheimer's disease brains

“…41 In addition, the expression of the glycosylation enzymes α2-fucosyltransferases (FUT1 and FUT2) are required in synapse formation and neurite outgrowth. 42,43 Up to 30% of the total mass of a voltage-gated sodium or potassium ion channel is N-linked glycans. 44 N-linked glycan modifications and ATP concentrations are utilized by a neuron to fine tune the membrane polarization and action potential transmission within an axon.…”

“…N‐linked glycans regulate neurotransmitter release and the formation of new synapses through the turnover and stability of brain glycoproteins such as synapsin 1 41 . In addition, the expression of the glycosylation enzymes α2‐fucosyltransferases (FUT1 and FUT2) are required in synapse formation and neurite outgrowth 42,43 . Up to 30% of the total mass of a voltage‐gated sodium or potassium ion channel is N‐linked glycans 44 .…”

Sec1 Regulates Intestinal Mucosal Immunity in A Mouse Model of Inflammatory Bowel Disease

“…Fut1/Fut2/Sec1 triple knockout mice with a complete de ciency of α(1, 2)fucosyltransferase has been recently generated and reported in a preprint; this triple knockout animals showed no de ciency in viability and development, no changes in colon microbiome but had a complete lack of H blood group antigen (15). Chen et al (2019) used a LoxP-neomycin-LoxP cassette to replace a 30 kb region that contains protein-coding regions of both Fut2 and Sec1 (15). Such a knockout strategy might have neglected the signi cance of Fut2 and Sec1 as individual genes for mouse IBD.…”

“…It is, however, reasonable to speculate that fut2 in mice may not fully represent its counterpart in humans as another neighboring gene, Sec1, was also found to be highly homologous to human FUT2. Fut1/Fut2/Sec1 triple knockout mice with a complete de ciency of α(1, 2)fucosyltransferase has been recently generated and reported in a preprint; this triple knockout animals showed no de ciency in viability and development, no changes in colon microbiome but had a complete lack of H blood group antigen (15). Chen et al (2019) used a LoxP-neomycin-LoxP cassette to replace a 30 kb region that contains protein-coding regions of both Fut2 and Sec1 (15).…”