Mice lacking the nucleoporin NUP210L and BAF-paralogue BAF-L are infertile with disorganized manchette microtubules that invaginate the spermatid nucleus

During spermiogenesis haploid round spermatids differentiate into spermatozoa, the highly specialized male gametes. This involves many morphogenic processes including nuclear elongation, chromatin compaction, cytoplasmic reduction, and formation of the acrosome and the flagellum. These events are orchestrated by cytoskeletal elements (acroplaxome and manchette) that attach to the nuclear envelope (NE) except at the caudal pole where the nuclear pore complexes (NPCs) shift to form a dense array. Here, we used genetic dissection to reveal unknown function at the caudal NE, through the study of two spermatid-specific proteins whose orthologues persist there during spermatid nuclear elongation in human: NUP210L, a transmembrane nucleoporin and BAF-L, paralogue of the chromatin protein BAF. In mice, inactivation of BAF-L or NUP210L has no impact on fertility. Here we present mice that are double knockout for BAF-L and NUP210L. We show that two copies of BAF-L become essential for fertility in mice lacking NUP210L. InNup210l-/-,Banf2+/-orNup210l-/-,Banf2-/-mice, most spermatids arrest during nuclear elongation (step 10-11), with mislocalization of NPCs and disorganization of manchette microtubules that often invaginate the nucleus from the caudal pole. Our results suggest that the NPC array and the chromatin ensure nuclear integrity at the caudal pole during spermatid nuclear remodeling.