Transgene Insertion Induced Dominant Male Sterility and Rescue of Male Fertility

Transgene insertions in the mouse often cause mutations at chromosomal loci. Analysis of insertion mutations that cause male sterility may lead to the identification of novel molecular mechanisms implicated in male fertility. Here we show a line of transgenic mice with dominant inheritance of male sterility (DMS) that was found amid several lines that were normally fertile. Transgene-positive males from this line invariably were sterile, whereas transgenic females and transgene-negative male littermates were fertile. Histologic analysis and TUNEL staining for apoptotic cells in DMS testis showed spermatogenesis arrest at metaphase of meiosis I (M-I), accompanied by massive apo-ptosis of spermatocytes. Meiosis I arrest was incomplete, how-ever, as small numbers of spermatids and spermatozoa were found. Both round spermatids and spermatozoa were evaluate