2026-04-17T07:42:01Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1723062025-12-05T09:34:38Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917
RECERCAT author Bao, Jianqiang author Perez, Carlos J. author Kim, Jeesun author Zhang, Huan author Murphy, Caitlin J. author Hamidi, Tewfik author Jaubert, Jean author Platt, Craig D. author Chou, Janet author Deng, Meichun author Zhou, Meng-Hua author Huang, Yuying author Gaitán Peñas, Héctor author Guenet, Jean-Louis author Lin, Kevin author Lu, Yue author Chen, Taiping author Bedford, Mark T. author Dent, Sharon Y. R. author Richburg, John H. author Estévez Povedano, Raúl author Pan, Hui-Lin author Geha, Raif S. author Shi, Qinghua author Benavides, Fernando G. 2020-11-24T14:14:37Z2020-11-24T14:14:37Z2018-08-232020-11-24T14:14:37Z Ion channel-controlled cell volume regulation is of fundamental significance to the physiological function of sperm. In addition to volume regulation, LRRC8A-dependent volume-regulated anion channel (VRAC) activity is involved in cell cycle progression, insulin signaling, and cisplatin resistance. Nevertheless, the contribution of LRRC8A and its dependent VRAC activity in the germ cell lineage remain unknown. By utilizing a spontaneous Lrrc8a mouse mutation (c.1325delTG, p.F443*) and genetically engineered mouse models, we demonstrate that LRRC8A-dependent VRAC activity is essential for male germ cell development and fertility. Lrrc8a-null male germ cells undergo progressive degeneration independent of the apoptotic pathway during postnatal testicular development. Lrrc8a-deficient mouse sperm exhibit multiple morphological abnormalities of the flagella (MMAF), a feature commonly observed in the sperm of infertile human patients. Importantly, we identified a human patient with a rare LRRC8A hypomorphic mutation (c.1634G>A, p.Arg545His) possibly linked to Sertoli cell-only syndrome (SCOS), a male sterility disorder characterized by the loss of germ cells. Thus, LRRC8A is a critical factor required for germ cell development and volume regulation in the mouse, and it might serve as a novel diagnostic and therapeutic target for SCOS patients. (c) American Society for Clinical Investigation, 2018 info:eu-repo/semantics/openAccess Esterilitat en els animals Anions Infertility in animals Anions Deficient LRRC8A-dependent volume-regulated anion channel activity is associated with male infertility in mice info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion