Overexpression of c-myc induces apoptosis at the prophase of meiosis of rat primary spermatocytes.
Transgenic rats expressing the rat c-myc gene under the control of the human metallothionein II A promoter were produced. We found that the female transgenic rats were fertile, but that the male transgenic rats were sterile. Atrophy of the seminiferous tubules and depletion of sperm were observed in the sterile male testes. The expression of differential stage-specific mRNAs, including those of the c-kit receptor proto-oncogene, meiotic heat-shock protein 70 gene, acrosin gene, and transition protein 1 gene, was analyzed by the reverse transcriptase-polymerase chain reaction during spermatogenesis. The results suggested that spermatogenesis in these sterile rats were arrested at the prophase of meiosis in the primary spermatocytes. We found that apoptotic DNA fragmentation occurred in primary spermatocytes of the sterile transgenic rats. These results suggest that overexpression of the c-myc gene induces apoptosis at the prophase meiosis of the primary spermatocytes thereby causing male sterility in the c-myc transgenic rats.
Kodaira
K
K
YS New Technology Institute, Inc., Tochigi, Japan.
Takahashi
R
R
Hirabayashi
M
M
Suzuki
T
T
Obinata
M
M
Ueda
M
M
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000503:physiopathology*; D008297:Male; D008540:Meiosis; D008668:Metallothionein / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011418:Prophase; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger; D051381:Rats; D013090:Spermatocytes / Q000502:physiology*; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D025721:WT1 Proteins
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors; D025721:WT1 Proteins; D008668:Metallothionein