Sperm head shaping is dependent upon the constriction of F-actin bundles found in the Sertoli cells of the testes and a cytoskeletal plate, the acroplaxome and its marginal ring found in the sperm head. The acroplaxome anchors the acrosomal vesicle to the sperm nuclear lamina. These differentiation processes as well as the coupling of the tail to the sperm head are known as spermiogenesis. Although the acroplaxome and its marginal ring are recognized as necessary structures for normal sperm development,the mechanism whereby they achieve this is poorly understood. Herein we describe a mouse line with a mutation in nonmuscle myosin II-A (NM II-A), E1841K, found in human MYH9-related disease. In addition to modeling MYH9-related disease male mice homozygous for the mutation (E1841K/E1841K) are infertile with no viable sperm in the epididymis. Histological analyses reveal severe sperm defects in the NM II-A E1841K/E1841K mouse testes that begin during spermiogenesis. Transmission electron microscopy shows aberrant spermatid elongation during which the acroplaxome and the acrosome fail to correctly extend and often show an abnormal wave-like appearance. Although these aberrantly elongated spermatids form a tail, they often fail to couple it to the spermatid head. Furthermore, immunofluorescence confocal microscopy of developing round spermatids shows localization of both wild-type and mutant NM II-A to the marginal ring of the acroplaxome. In vitro experiments using baculovirus-expressed NM II show abnormal filament formation of the NM II-A E1841K mutants compared to wild-type. The filaments formed by the mutant myosin are irregular and have a larger mean width and length than wild type. These results suggest that the mutant NM II-A filaments form a defective marginal ring leading to abnormal sperm head shaping. Although the mechanism whereby the NM II-A E1841K mutation affects the coupling of the sperm tail remains unclear, our observations both in-vivo and in-vitro suggest a previously unknown role for NM II-A in sperm head shaping and male fertility.
