E-MAP-115, encoding a microtubule-associated protein, is a retinoic acid-inducible gene required for spermatogenesis

Cell type-specific microtubules, such as the Sertoli cell microtubules and the manchette and flagellum microtubules of the spermatids, play essential roles in spermatogenesis. We identified the gene encoding E-MAP-115 (epithe lial microtubule-associated protein of 115 kD) as a retinoic acid-inducible gene using gene trap mutagenesis in mouse embryonic stem cells. The gene t rap insertion led to a null allele of the E-MAP-115 gene and, in agreement with its high expression in the testis, male mice homozygous for the mutati on were sterile because of deformation of spermatid nuclei and subsequent g radual loss of germ cells. Consistent with a possible role for E-MAP-115 in stabilizing microtubules, microtubule associations in the mutant were morp hologically abnormal in the manchette of spermatids and in Sertoli cells. W e hypothesize that the abnormal microtubules in these two cell types are re sponsible for deformation of spermatid nuclei and germ cell loss, respectiv ely, and indicate an essential role for E-MAP-115 in microtubule functions required for spermatogenesis.