Collaborator of ARF (CARF) regulates cell proliferative fate through both p53-dependent and -independent mechanisms. Recently, we reported a new function of CARF as a positive regulator of Wnt signaling. Despite these findings, the physiological function of CARF has not been well studied. Here, we generated CARF knockout mice and found that male CARF−/− mice exhibited significantly impaired fertility and Sertoli-cell-only (SCO) syndrome phenotypes. Further studies revealed that loss of CARF in Sertoli cells led to decreased GDNF expression, which hindered spermatogonial stem cells (SSCs) self-renewal. Meanwhile, CARF loss in undifferentiated spermatogonia impaired their proliferation. These two mechanisms together led to SCO syndrome phenotypes, which could be functionally rescued by pharmacological or genetic reactivation of Wnt signaling. Finally, we identified CARFS351F as a potential pathogenic mutation in an SCO patient. Overall, our findings reveal important roles of CARF in spermatogonial self-renewal and proliferation through the Wnt signaling pathway.
University library takes an important role in education and research to drive higher education development and promote to accomplish its missions. We analyzed some common problems in the utilization of university library resources, including information supply, knowledge popularization and characteristic service based on close relationship between library resource utilization and university development and its great significance. Taking relevant experiences of libray at China Three Gorges University for example, this essay discussed the innovative method of utilizing university library resource, including setting up "the second classroom", providing venture information, strengthening the training of resource supply, carrying on academic lectures etc. to promote the development of talent cultivation, scientific research and social services in university.
In the title compound, C37H40N4O2, the xanthene and spirolactam rings are almost planar, with r.m.s. deviations from the mean planes of 0.223 (2) and 0.057 (2) Å, respectively, and form a dihedral angle of 85.76 (3)°. The dihedral angle between the xanthene mean plane and the benzene ring is 87.16 (5)°. One of the two ethyl groups of one of the diethylamino groups is disordered over two sets of sites [0.76 (1):0.24 (1)].
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