Regulation of protamine 1 expression during spermatogenesis in transgenic mice

A characteristic feature of nuclear maturation during spermatogenesis in virtually all vertebrate organisms is the replacement of histones by a class of small, extremely basic proteins known collectively as the protamines. Mouse sperm nuclei contain two structurally distinct protamine variants, mP1 and mP2. The mP1 gene is transcribed exclusively in round spermatids and not translated until these cell have differentiated into elongated spermatids.;The mP1 gene was cloned using oligonucleotide probes and characterized by DNA sequence analysis. Transgenic mice harboring a marked version of the mP1 gene, mP1;The pattern of hGH protein accumulation within the seminiferous epithelium, and the temporal profile of hGH accumulation during prepuberal testis development in transgenic mice harboring various mP1-human growth hormone chimeric genes were examined immunocytochemically. Translation of a chimeric hGH transcript containing mP1 5;The mP1:mP2 protein ratio in elongated spermatid nuclei is increased by overproduction of mP1 mRNA in transgenic mice. Distorted mP1:mP2 ratios are not observed in transgenic nuclei of epididymal sperm, suggesting that a post-translational, intra-nuclear mechanism exists to establish the mP1:mP2 ratio of mature sperm.;Sequences within mP1 and the SV40 T-antigen gene interact to direct the expression of an mP1-SV40 chimeric gene to round spermatids, the heart and the temporal bone in multiple lines of transgenic mice. As a consequence of ectopic mP1-SV40 expression, these mice develop rhabdomyosarcomas and osteosarcomas. No testicular pathology is observed.