FLAGELLAR AND ACROSOMAL ABNORMALITIES ASSOCIATED WITH TESTICULAR HSV-TK EXPRESSION IN THE MOUSE

Expression of herpes simplex virus thymidine kinase (HSV-tk) in transg enic mouse testis is associated with abnormalities in spermatogenesis leading to infertility. Our studies of this phenomenon in two transgen ic lines led to the identification of a genetic locus that reduced tes ticular HSV-tk activity and restored fertility. Using light and electr on 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 aberra tions, and a developmental arrest in spermatogenesis. Infertile males from line ANF1 had lower levels of testicular HSV-tk expression and de monstrated a unique set of structural changes present in the neck and flagellum of epididymal sperm. Revertant ANF1 males, with a significan t decrease in testicular HSV-tk expression and a restoration of fertil ity, showed a marked reduction in the number of sperm abnormalities. S everal of the ANF1-specific abnormalities were similar to lesions repo rted in the sperm of mouse t locus mutants, mouse wobbler homozygotes, and bulls with the Dag-defect.