Pattern and frequency of nocodazole induced meiotic nondisjunction in oocytes of mice carrying the 'tobacco mouse' metacentric Rb(16.17)7Bnr.
Oocytes from (C3H/HeH x 101/H)F1 and Rb(16.17)7Bnr homozygous females were exposed to a range of doses of nocodazole in vitro. The spindle poison caused a dose dependent increase in metaphase I (MI) arrest and hyperploidy. A concentration of 0.03 microgram/ml was found to induce a maximum hyperploid frequency of 3.1% and 11.6% respectively without a high level of MI arrest. Between 0.03 and 0.05 microgram/ml MI arrest increased substantially and reached a frequency of approximately 90%. In a further experiment oocytes from Rb7 homozygous, heterozygous and 3H1 females were exposed to 0.03 microgram/ml nocodazole 4, 6 or 8 h after the onset of maturation. The phase at which the spindle was inhibited resulted in a specific pattern of nondisjunction which in turn was dependent on whether the female carried an Rb metacentric. 3H1 oocytes gave a normally distributed pattern of increase in aneuploid frequency (over the spontaneous value) centering around a 6 h application. This was thought to be due to the interaction of chromosomes with the microtubules of the spindle during attachment and/or alignment. In contrast both Rb homozygotes and heterozygotes gave the same biphasic response, with a high frequency of aneuploidy in the oocytes when nocodazole was applied 4 and 8 h after the onset of maturation. In Rb homozygotes we demonstrated that the Rb bivalent underwent nondisjunction more frequently than the average acrocentric, when nocodazole was administered early.(ABSTRACT TRUNCATED AT 250 WORDS)
Everett
C A
CA
Department of Obstetrics and Gynaecology, University of Edinburgh, U.K.
Searle
J B
JB
D000705:Anaphase / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002503:Centromere; D002875:Chromosomes / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D008540:Meiosis / Q000187:drug effects* / Q000235:genetics; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D015739:Nocodazole / Q000494:pharmacology*; D009630:Nondisjunction, Genetic; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011123:Polyploidy; D008941:Spindle Apparatus / Q000187:drug effects; D013997:Time Factors
D000970:Antineoplastic Agents; D015739:Nocodazole