Specific arrest of spermatogenesis caused by apoptotic cell death in transgenic mice.
BACKGROUND
The c-myc protooncogene has been implicated in the control of cell proliferation, differentiation and/or apoptosis in various cellular systems. However, the role of c-myc in germ cell lineage is largely unknown.


RESULTS
We have produced transgenic mouse lines carrying the rat c-myc protooncogene under the control of human metallothionein promoter (hMT-c-myc). It was found that the male transgenic mice were sterile. In contrast, all of the female transgenic mice were completely fertile and transmitted the transgene to the next generation. However, male transgenic mice from the female transgenic founders were also found to be sterile. This sterility was due to a defect in spermatogenic cell differentiation, since virtually no sperm were seen within the seminiferous tubules or the cauda epididymis. Histological examination revealed that germ cell death occurred approximately 7 days after birth and, consequently, spermatogenesis was arrested at an early stage in meiotic division in the transgenic mice. Moreover, this germ cell death was found to be caused by apoptosis.


CONCLUSIONS
We conclude that an excess level of c-myc expression in differentiating spermatogenic cells is responsible for the apoptotic death of germ cell, and that a decrease in c-myc level would be an obligatory step for the completion of normal spermatogenesis.
Suzuki
M
M
Furusawa MorphoGene Project, Research Development Corporation of Japan, ERATO, Tsukuba, Japan.
Abe
K
K
Yoshinaga
K
K
Obinata
M
M
Furusawa
M
M
Abe
K
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D007246:Infertility / Q000235:genetics / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000473:pathology; D013737:Testis / Q000473:pathology; D019076:Transgenes / Q000235:genetics
D016271:Proto-Oncogene Proteins c-myc; D012313:RNA; D008668:Metallothionein