ANALYSIS OF THE MECHANISM(S) OF METAPHASE-I ARREST IN STRAIN LT MOUSEOOCYTES - PARTICIPATION OF MOS

Oocytes of almost all vertebrates become arrested at metaphase II to a wait fertilization. Arrest is achieved with the participation of a pro tein complex known as cytostatic factor (CSF) that stabilizes histone H1 kinase activity. MOS and mitogen-activated protein kinase (MAPK) ar e important components of CSF, Strain LT/Sv mice, and strains related to LT/Sv, produce a high percentage of atypical oocytes that are arres ted at metaphase I when normal oocytes have progressed to metaphase II . The potential role of MOS in metaphase I arrest was investigated usi ng strain LT/Sv and LT-related recombinant inbred strains, LTXBO and C X8-4. MOS and MAPK are produced and functional in maturing LT oocytes, Two experimental paradigms were used to reduce or delete MOS in LT oo cytes and assess effects on metaphase I arrest. First, sense and antis ense 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 Mo s null mutation were crossed with LT mice, the null mutation was backc rossed three times to LT mice, and Mos(+/-) N-3 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-dependen t mechanism. However, unlike Mos(+/+) and Mos(+/-) CX8-4 N3F1 oocytes. metaphase I arrest of Mos(-/-) CX8-4 N3F1 oocytes was not sustained a fter 17 hours and became reversed gradually. These results, like the a ntisense Mos oligonucleotide microinjection experiments, suggest that MOS participates in sustaining metaphase I arrest in LT oocytes.