title: Loss of Bmyc results in increased apoptosis associated with upregulation of Myc expression in juvenile murine testis.
abstract: Bmyc is a member of the Myc family of transcriptional regulators in the mouse and the rat. It is predominantly expressed in hormonally controlled tissues, with highest level of expression in the epididymis. The BMYC protein has been shown to function as a transcription factor in vitro and to inhibit MYC. To study the significance of BMYC in vivo, a Bmyc knockout (KO) mouse model was generated by homologous recombination. The KO mice were viable and fertile and did not display gross morphological or histological changes compared to the WT mice. However, the testes and the epididymides of the KO mice were smaller than those of the WT mice. Correspondingly, a tendency for a lower sperm concentration in the cauda epididymides of the KO mice was detected. The testosterone produced/testis was significantly reduced, and accordingly, the LH levels were increased in the KO mice. Also, the expression levels of Myc and several of its target genes were elevated in the testes of prepubertal KO mice, whereas no differences in gene expression levels were detected in adult mice. Associated with the increased Myc expression, more apoptotic spermatogenic cells were detected in the seminiferous tubules of the KO mice. In conclusion, our data suggest that Bmyc is a regulator of Myc in vivo and that overexpression of Myc in the developing testis leads to increased apoptosis of spermatogenic cells.
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland.
authors.forename: Heikki T
authors.initials: HT
authors.lastname: Turunen
authors.forename: Petra
authors.initials: P
authors.lastname: Sipilä
authors.forename: Leena
authors.initials: L
authors.lastname: Strauss
authors.forename: Ida
authors.initials: I
authors.lastname: Björkgren
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D046528:Chimerism; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009845:Oligospermia / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012671:Seminiferous Tubules / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C431443:Bmyc protein, mouse; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc