Faculty Research 1990 - 1999

Title

Analysis of the mechanism(s) of metaphase I arrest in strain LT mouse oocytes: participation of MOS.

Document Type

Article

Publication Date

1997

Keywords

Ca(2+)-Calmodulin-Dependent-Protein-Kinase: me, Cells-Cultured, Crosses-Genetic, Meiosis: ph, Metaphase: ph, Mice, Mice-Inbred-C57BL, Mice-Mutant-Strains, Oligonucleotides-Antisense, Oocytes: en, cy, me, Proto-Oncogene-Proteins-c-mos: bi, ge, ph, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Development 1997 Dec;124(24):5107-13

Grant

CA62392/CA/NCI, CA34196/CA/NCI

Abstract

Oocytes of almost all vertebrates become arrested at metaphase II to await fertilization. Arrest is achieved with the participation of a protein complex known as cytostatic factor (CSF) that stabilizes histone H1 kinase activity. MOS and mitogen-activated protein kinase (MAPK) are important components of CSF. Strain LT/Sv mice, and strains related to LT/Sv, produce a high percentage of atypical oocytes that are arrested at metaphase I when normal oocytes have progressed to metaphase II. The potential role of MOS in metaphase I arrest was investigated using strain LT/Sv and LT-related recombinant inbred strains, LTXBO and CX8-4. MOS and MAPK are produced and functional in maturing LT oocytes. Two experimental paradigms were used to reduce or delete MOS in LT oocytes and assess effects on metaphase I arrest. First, sense and antisense Mos oligonucleotides were microinjected into metaphase I-arrested oocytes. Antisense, but not sense, Mos oligonucleotides promoted the activation of metaphase I-arrested oocytes. Second, mice carrying a Mos null mutation were crossed with LT mice, the null mutation was backcrossed three times to LT mice, and Mos(+/-) N3 mice were intercrossed to produce Mos(-/-), Mos(+/-) and Mos(+/+) N3F1 mice. Oocytes of all three Mos genotypes of N3F1 mice sustained meiotic arrest for 17 hours indicating that metaphase I arrest is not initiated by a MOS-dependent mechanism. However, unlike Mos(+/+) and Mos(+/-) CX8-4 N3F1 oocytes, metaphase I arrest of Mos(-/-) CX8-4 N3F1 oocytes was not sustained after 17 hours and became reversed gradually. These results, like the antisense Mos oligonucleotide microinjection experiments, suggest that MOS participates in sustaining metaphase I arrest in LT oocytes.

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