Over the entire period studied we did not observe decreased transcript levels for vimentin as claimed by other investigators. Nonetheless, clear differences in the localization of vimentin staining were seen in SC of SCARKO and control mice. In control animals the vimentin cytoskeleton surrounded the SC nuclei with extensions directed towards the center of the tubules. In the SCARKO testis, and particularly in cells with centrally located nuclei, vimentin was mainly found in anchor-like structures connecting the lower pole of the nucleus to the most peripheral part of the tubule close to the basal lamina. Whether this change is causally related to the absence of androgen action or whether it is just a reflection of the lack of normal cell polarization remains to be investigated. A search for new potentially relevant androgen target genes related to cell adhesion and cytoskeletal dynamics that might be differentially expressed in SCARKO and control animals during early puberty, revealed at least 6 candidates. ACTN3 is a cytoskeletal actin-binding protein and a member of the spectrin superfamily. It is found in anchoring junctions and, besides binding to actin filaments, it associates with cytoskeletal elements, signaling molecules and with the cytoplasmic domains of transmembrane proteins and ion channels. ANK3 is a member of the ankyrin protein family and links integral membrane proteins to the spectrin-based cytoskeleton. It is thought to play a role in the polarized distribution of proteins to specific subcellular sites. ANXA9 belongs to the annexins, a family of evolutionary conserved proteins characterized by their ability to interact with membrane phospholipids in a Ca ++ -dependent way. These proteins have been implicated in membrane organization, membrane-cytoskeleton contacts and vesicular transport. A unique feature of ANXA9 is that its Ca +binding sites are dysfunctional and accordingly its function is unknown. Interestingly, its promoter binds GATA1, an important transcription factor in SC, the expression of which we monitored in our samples. SCIN is an actin-severing protein reported typically in tissues demonstrating a high secretory activity. In bovine SC it was shown to accumulate within the cytoplasm near the base of the cells in a stage-specific manner suggesting a potential role in the Chlorhexidine hydrochloride regulation of tight junction permeability. EMB is a cell adhesion molecule belonging to the immunoglobulin superfamily and involved in cell-extracellular matrix interactions during development. Increased expression has been correlated with the appearance of highly organized luminal and ductal structures. Its congener basigin also seems to be involved in the translocation of monocarboxylate transporters to the plasma membrane. MPZL2 is also a member of the immunoglobulin superfamily expressed in various epithelia. It has been shown to mediate cell adhesion through homophilic interaction and some data Lomitapide Mesylate suggest association with the cytoskeleton. Interestingly, recent data point to a role in the control of the permeability of the blood-cerebrospinal fluid barrier. For all of these genes, we present evidence that SC are their main or only site of cellular localization, indicating that they may contribute to the observed effects of the SC AR on cell maturation, cell interactions and tubular restructuring. In conclusion, targeted ablation of AR from SC does not completely prevent the formation of an anatomical and functional barrier defining basal and adluminal compartments within the seminiferous epithelium. However, barrier formation is delayed and defects are observed in many tubules. The defective barrier formation is accompanied by disturbances in the nuclear maturation process and in SC polarization resulting in aberrant positioning of cytoskeletal elements such as vimentin. The observed developmental defects in SCARKO SC are accompanied by disturbances in the expression of well known molecules involved in cell adhesion and cytoskeleton building.