SPONTANEOUS RATES OF SEX CHROMOSOMAL ANEUPLOIDIES IN SPERM AND OFFSPRING OF MICE - A VALIDATION OF THE DETECTION OF ANEUPLOID SPERM BY FLUORESCENCE IN-SITU HYBRIDIZATION

This study was designed to evaluate the frequency of aneuploid sperm i n young adult mice of the genotype (102/E1 X C3H/E1)F-1 determined by the fluorescence in situ hybridization (FISH) procedure and to evaluat e the frequencies of aneuploid sperm observed by FISH compared with th e frequencies of aneuploid offspring. Three-chromosome FISH was applie d to determine the fractions of hyperhaploid and diploid sperm with DN A probes specific for chromosomes X, Y and 8. The animals were treated with three common solvents. Sperm smears were prepared for FISH by tw o similar protocols and were scored by different persons and in two di fferent laboratories. There were no significant differences between sc orers or laboratories. The frequencies of the sex chromosome aneuploid ies in sperm (Y-Y and X-Y) were compared to the frequencies of mice ca rrying sex chromosome aneuploidy among controls of the heritable trans location assay in studies conducted from 1975-1995. To identify aneupl oid individuals, untreated males and females of the genotype (102/E1 X C3H/E1)F-1 were mated to assess their fertility by observing three co nsecutive litters. Semisterile and sterile animals were further analys ed by meiotic cytogenetics and by karyotyping to determine the inciden ce of reciprocal translocations and sex chromosome aneuploidies (XXY a nd XYY). Based on the analysis of 175247 sperm and 9840 progeny, the f requency of Y-Y sperm was 0.01% while 0.03% of the offspring were XYY. The frequency of X-Y sperm was 0.005% while 0.02% of the offspring we re XXY. The frequencies of aneuploid sex chromosomes were not signific antly different between sperm and offspring. This allows two conclusio ns. First, there was no detectable prenatal selection against these se x-chromosomal aneuploid offspring, and second, germ cell aneuploidy ca n be reliably determined in mice by sperm FISH analyses.