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 (epithelial microtubule-associated protein of 115 kD) as a retinoic acid-inducible gene using gene trap mutagenesis in mouse embryonic stem cells. The gene trap 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 mutation were sterile because of deformation of spermatid nuclei and subsequent gradual loss of germ cells. Consistent with a possible role for E-MAP-115 in stabilizing microtubules, microtubule associations in the mutant were morphologically abnormal in the manchette of spermatids and in Sertoli cells. We hypothesize that the abnormal microtubules in these two cell types are responsible for deformation of spermatid nuclei and germ cell loss, respectively, and indicate an essential role for E-MAP-115 in microtubule functions required for spermatogenesis.
Komada
M
M
Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 USA.
McLean
D J
DJ
Griswold
M D
MD
Russell
L D
LD
Soriano
P
P
D000818:Animals; D008297:Male; D051379:Mice; D015152:Blotting, Northern; D002478:Cells, Cultured; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D017403:In Situ Hybridization; D007246:Infertility / Q000235:genetics; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008870:Microtubules / Q000378:metabolism / Q000502:physiology; D016296:Mutagenesis; D009154:Mutation; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis; D013234:Stem Cells / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism; D015854:Up-Regulation
D008869:Microtubule-Associated Proteins; D014212:Tretinoin; C000721970:MAP7 protein, mouse