In vivo role of alpha-mannosidase IIx: ineffective spermatogenesis resulting from targeted disruption of the Man2a2 in the mouse.
Alpha-mannosidase IIx (MX) is an enzyme closely related to the Golgi N-glycan processing enzyme alpha-mannosidase II (MII). The enzymatic activity of MX in vitro is minimal. Therefore, the in vivo role of MX in N-glycan processing is as yet unclear. The targeted disruption of the gene encoding MX in the mouse resulted in an obvious phenotype, i.e., MX-deficient males were found to be infertile. Testes from homozygous mutant male mice are smaller than those from wild-type or heterozygous littermates. Histology of the MX null mouse testis showed significant reduction of spermatogenic cells in the seminiferous tubules. Electron microscopy showed that prominent intercellular spaces surround MX-deficient spermatogenic cells, suggesting a failure of germ cell adhesion to Sertoli cells. Quantitative structural analyses of N-glycans from wild-type and MX-deficient mouse testis showed that wild-type testes contain GlcNAc-terminated complex type N-glycans, while they are significantly reduced in MX-deficient mutant testis. An in vitro assay for adhesion of spermatogenic cells to Sertoli cells was carried out. By testing the effect of each purified N-glycan oligosaccharide, it was demonstrated that a GlcNAc-terminated tri-antennary, fucosylated N-glycan has an activity on the adhesion between germ cells and Sertoli cells. Thus, the targeted disruption of the gene encoding MX uncovered a novel carbohydrate recognition system in a biologically important process, spermatogenesis.
Fukuda
Michiko N
MN
The Burnham Institute, La Jolla, CA 92037, USA. michiko@burnham-inst.org
Akama
Tomoya O
TO
D000818:Animals; D018390:Gene Targeting; D006801:Humans; D008297:Male; D008361:Mannosidases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011134:Polysaccharides / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology*
D011134:Polysaccharides; D008361:Mannosidases; C445059:MAN2A2 protein, human; C499170:Man2a2 protein, mouse