| Symplastic spermatids (sys) mice contain a single transgene insertion, which causes a recessive mutation that results in reproductive defects in both sexes. Males are sterile due to a defect in spermatogenesis. During spermiogenesis, adhesion between spermatids and Sertoli cells is lost and the intercellular bridges that link clones of haploid germ cells widen so multi-nucleated spermatids (symplasts) are observed. In females, mammary glands are enlarged during prepubertal development and the infiltration of the ductal epithelium is retarded. Milk is poorly secreted following pregnancy and histology reveals accumulation of vacuoles in mammary epithelial cells. The sys mutation is a 1.24 Mb deletion of mouse chromosome 14. Comparative genome analysis was used to show that Fibronectin-domain containing protein 3a (Fndc3a) is the only gene deleted in the sys mutation. The sys mutation failed to complement a gene-trap mutation within the Fndc3a locus, confirming that Fndc3a is the cause of male sterility in sys homozygotes. Fndc3a is predicted to encode a 1198 as polypeptide with three structural domains; a proline-rich N-terminus that contains consensus WW and SH3 binding domains, nine fibronectin type-III domains, and a hydrophobic COOH-terminus. Fndc3a is a member of a novel gene family with three members in mouse (Fndc3a , Fndc3b, and Fndc3c). Northern and western analyses indicate that Fndc3a is expressed in testis, mammary gland, and other tissues. The highest steady-state expression was observed in organs with exocrine functions. FNDC3A is an integral membrane protein that localizes to the ER in COS-7 cells and to the acrosome in spermatids within the adult testis. My data suggests that Fndc3a mediates fusion of exocytotic vesicles with the plasma membrane, and this is presented as a model. |
