Huttner K M, Pudney J, Milstone D S, Ladd D, Seidman J G
Howard Hughes Medical Institute, Boston, Massachusetts.
Biol Reprod. 1993 Aug;49(2):251-61. doi: 10.1095/biolreprod49.2.251.
Expression of herpes simplex virus thymidine kinase (HSV-tk) in transgenic mouse testis is associated with abnormalities in spermatogenesis leading to infertility. Our studies of this phenomenon in two transgenic lines led to the identification of a genetic locus that reduced testicular HSV-tk activity and restored fertility. Using light and electron microscopy, we examined spermatogenesis in the infertile transgenic males as well as in the fertile revertants. Infertile males from line 21OH1 had high levels of testicular HSV-tk activity, acrosomal aberrations, and a developmental arrest in spermatogenesis. Infertile males from line ANF1 had lower levels of testicular HSV-tk expression and demonstrated a unique set of structural changes present in the neck and flagellum of epididymal sperm. Revertant ANF1 males, with a significant decrease in testicular HSV-tk expression and a restoration of fertility, showed a marked reduction in the number of sperm abnormalities. Several of the ANF1-specific abnormalities were similar to lesions reported in the sperm of mouse t locus mutants, mouse wobbler homozygotes, and bulls with the Dag-defect.
单纯疱疹病毒胸苷激酶（HSV-tk）在转基因小鼠睾丸中的表达与精子发生异常相关，进而导致不育。我们对两个转基因品系中这一现象的研究，确定了一个遗传位点，该位点可降低睾丸HSV-tk活性并恢复生育能力。我们利用光学显微镜和电子显微镜，检查了不育转基因雄性小鼠以及可育回复体的精子发生情况。21OH1品系的不育雄性小鼠睾丸HSV-tk活性水平高，顶体畸变，精子发生存在发育停滞。ANF1品系的不育雄性小鼠睾丸HSV-tk表达水平较低，附睾精子颈部和鞭毛出现一组独特的结构变化。睾丸HSV-tk表达显著降低且生育能力恢复的ANF1回复体雄性小鼠，精子异常数量明显减少。ANF1品系的一些特异性异常与小鼠t位点突变体、小鼠震颤纯合子以及患有达格缺陷的公牛精子中报道的病变相似。
