The sperm acrosome is essential for sperm-egg fusion and is often defective
in men with nonobstructive infertility. Here we report that mate mice with
a null mutation in Hrb are infertile and display round-headed spermatozoa
that Lack an acrosome. In wild-type spermatids, Hrb is associated with the
cytosolic surface of proacrosomic transport vesicles that fuse to create a
single Large acrosomic vesicle at step 3 of spermiogenesis. Although proacr
osomic vesicles form in spermatids that lack Hrb, the vesicles are unable t
o fuse, blocking acrosome development at step 2. We conclude that Hrb is re
quired for docking and/or fusion of proacrosomic vesicles during acrosome b
iogenesis.