Insertional mutation that causes acrosomal hypo-development: its relationship to sperm head shaping.

A family of transgenic mice (OVE 219) was generated by microinjection of a tyrosinase minigene (Ty811C). The transgenic mice demonstrate an atypical and variable coat color pattern and the homozygous males show abnormalities of spermatogenesis that are variably expressed from animal to animal. Heterozygous mice proved to have normal spermatogenesis and along with non-transgenic mice were used as controls to study the abnormalities in spermatogenesis in OVE 219 homozygous males. These abnormalities shed light on the features controlling normal spermatogenesis. In some homozygous males early spermiogenesis was disrupted as the flagellar microtubules became disorganized within the flagellar process. What appeared to be crystalline tubulin was noted within some of the rounded flagellar processes. Sperm with this defect did not develop a flagellum. In other homozygous males defects were apparent by step 6 or 7 of spermiogenesis when the acrosome did not grow and spread over the nucleus as noted in control animals. The modified nuclear envelope underlying the acrosome continued to develop and spread well beyond one margin of the acrosome. Since the modified nuclear envelope grew independently of the acrosome, the acrosome was not the controlling factor in determining the spread of the modified nuclear envelope. Micrographs revealed that Sertoli ectoplasmic specialization failed to form over most regions of the spermatid head lacking a normal acrosome. In homozygous males, the manchette took origin (proximally) in close relation to the modified nuclear envelope and never in relation to the edge of the spreading acrosome, a feature indicating that manchette placement was influenced by the position of the modified nuclear envelope and not the edge of the acrosome. Thus the modification in the nuclear envelope may be the primary event to signal acrosomal spread and manchette development. In spermatids where the manchette developed from an ectopic site, the result was abnormal caudal head shaping. In some spermatids a portion of the manchette was lacking. When this occurred the caudal head was rounded in the region of the missing manchette. In a minority of spermatids there was no evidence for a manchette. The entire caudal head was gently rounded. These data support the growing body of evidence that the caudal sperm head is shaped, in part, by the manchette. The OVE 219 family of mice provides a useful model to understand the processes involved in periods of spermiogenesis that are critical to development of a normally shaped sperm head.