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Molecular and Cellular Biology, November 2004, p. 9920-9929, Vol. 24, No. 22
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.22.9920-9929.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Inactivation of the Mgat1 Gene in Oocytes Impairs Oogenesis, but Embryos Lacking Complex and Hybrid N-Glycans Develop and Implant

Shaolin Shi,1 Suzannah A. Williams,1 Antti Seppo,1,{dagger} Henry Kurniawan,1 Wei Chen,1,{ddagger} Zhengyi Ye,2 Jamey D. Marth,2 and Pamela Stanley1*

Department of Cell Biology, Albert Einstein College of Medicine, New York, New York,1 Department of Medicine, University of California at San Diego and Howard Hughes Medical Institute, San Diego, California2

Received 10 June 2004/ Returned for modification 15 August 2004/ Accepted 24 August 2004

Complex and hybrid N-glycans contain sugar residues that have been implicated in fertilization, compaction of the embryo, and implantation. Inactivation of the Mgat1 gene responsible for their synthesis is embryonic lethal, but homozygous mutant blastocysts are phenotypically normal due to the presence of maternal Mgat1 gene transcripts. To identify roles for complex and hybrid N-glycans in oogenesis and preimplantation development, the Mgat1 gene in oocytes was deleted by using a ZP3Cre recombinase transgene. All mutant oocytes had an altered zona pellucida (ZP) that was thinner than the control ZP, and they did not possess complex N-glycans but contained ZP1, ZP2, and ZP3 glycoproteins. Mutant eggs were fertilized, all embryos implanted, and heterozygotes developed to birth. However, mutant females had decreased fertility, yielded fewer eggs after stimulation with gonadotropins, and produced a reduced number of preimplantation embryos and less progeny than controls. About 25% of embryonic day 3.5 (E3.5) embryos derived from mutant eggs were severely retarded in development, even when they were heterozygous and expressed complex N-glycans. Thus, a proportion of Mgat1–/– oocytes were developmentally compromised. Surprisingly, mutant eggs also gave rise to Mgat1–/– embryos that developed normally, implanted, and progressed to E9.5. Therefore, complex or hybrid N-glycans are required at some stage of oogenesis for the generation of a developmentally competent oocyte, but fertilization, blastogenesis, and implantation may proceed in their absence.

* Corresponding author. Mailing address: Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., New York, NY 10461. Phone: (718) 430-3346. Fax: (718) 430-8574. E-mail: stanley{at}aecom.yu.edu.

{dagger} Present address: Ikonisys, Inc., New Haven, CT 06511.

{ddagger} Present address: Laboratory Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10021.

Molecular and Cellular Biology, November 2004, p. 9920-9929, Vol. 24, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.22.9920-9929.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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