{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:17:36Z","timestamp":1789406256091,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T00:00:00Z","timestamp":1153180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Niemann\u2013Pick C1 (<jats:italic>NPC1<\/jats:italic>) gene encodes for a multiple membrane spanning protein, which regulates the trafficking of low\u2010density lipoprotein\u2010mediated endocytosed cholesterol. Mutation of the human <jats:italic>NPC1<\/jats:italic> gene causes Niemann\u2013Pick type C (NPC) disease. The <jats:italic>Npc1<jats:sup>NIH<\/jats:sup><\/jats:italic> mice, a model of human NPC disease, bear a spontaneous mutation of the <jats:italic>Npc1<\/jats:italic> gene, and are infertile. In this study, we have performed sperm analysis to search for the cause of male infertility in the <jats:italic>Npc1<jats:sup>NIH<\/jats:sup><\/jats:italic> mouse. The number of cauda sperms in <jats:italic>Npc1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice was decreased roughly three\u2010and\u2010half\u2010fold of that in wild\u2010type mice. The decreased sperm number in <jats:italic>Npc1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice is due, at least in part, to partial arrest of spermatogenesis in the testes, as revealed by histological analysis. Compared to wild\u2010type sperm, <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> sperm displayed a high frequency of morphological abnormalities, including tailless heads and aberrant heads. In the in vitro fertilization (IVF) assay using cumulus\u2010intact eggs, <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> sperm failed to produce two\u2010cell embryos. In the IVF assay where zona\u2010free eggs were used, <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> sperm bound normally but could not fuse with the egg. Further analysis indicated that <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> sperms are drastically impaired in the binding to the egg zona pellucida, only 14% of the level of wild\u2010type sperm. Moreover, on <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> cauda sperm, one\u2010third of the total cyritestin protein was not proteolytically processed, while fertilin \u03b2 was processed normally. Taken together, these results demonstrate that there are multiple defects in sperms from mice lacking a functional NPC1 protein, and these observed sperm defects may result in sterility. Mol. Reprod. Dev. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrd.20559","type":"journal-article","created":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T16:25:14Z","timestamp":1153239914000},"page":"1284-1291","source":"Crossref","is-referenced-by-count":32,"title":["Sperm defects in mice lacking a functional Niemann\u2013Pick C1 protein"],"prefix":"10.1002","volume":"73","author":[{"given":"Jun","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Akabane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie N.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Zhang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,26]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.228"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5384.1857"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13612"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.10093"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/8.4.297"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0323"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod52.2.211"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03362"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.031252"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-0952-7_5"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.1.00163"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.50.571"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401947101"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0297-201"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.232"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216500"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/beem.2000.0084"},{"key":"e_1_2_1_19_1","first-page":"140","article-title":"Lysosome lipid storage disorder in NCTR\u2010BALB\/c mice. 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