{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:57:07Z","timestamp":1775912227784,"version":"3.50.1"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T00:00:00Z","timestamp":1545264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0208835","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T18:39:43Z","timestamp":1545331183000},"page":"e0208835","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neurofibromin haploinsufficiency results in altered spermatogenesis in a mouse model of neurofibromatosis type 1"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4105-5705","authenticated-orcid":true,"given":"Harleen","family":"Chohan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-7781","authenticated-orcid":true,"given":"Mitra","family":"Esfandiarei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darian","family":"Arman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine D.","family":"Van Raamsdonk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis","family":"van Breemen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan M.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly A.","family":"Jett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,12,20]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/GIM.0b013e3181bf15e3","article-title":"Clinical and genetic aspects of neurofibromatosis 1","volume":"12","author":"K Jett","year":"2010","journal-title":"Genetics in medicine: official journal of the American College of Medical Genetics"},{"key":"ref2","article-title":"A Clinical, Pathologicala and Genetic Study of Multiple Neurofibromatosis","author":"SW Crowe FW","year":"1956"},{"issue":"11","key":"ref3","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1136\/jmg.26.11.712","article-title":"A genetic study of von Recklinghausen neurofibromatosis in south east Wales. II. Guidelines for genetic counselling","volume":"26","author":"SM Huson","year":"1989","journal-title":"Journal of medical genetics"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1601-5223.1988.tb00297.x","article-title":"Relative fertility and mutation rate in neurofibromatosis","volume":"108","author":"B Samuelsson","year":"1988","journal-title":"Hereditas"},{"issue":"2","key":"ref5","first-page":"84","article-title":"Neurofibromatosis in Gothenburg, Sweden. III. Psychiatric and social aspects","volume":"2","author":"B Samuelsson","year":"1989","journal-title":"Neurofibromatosis"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/BF00220540","article-title":"Genetics of neurofibromatosis 1 in Japan: mutation rate and paternal age effect","volume":"89","author":"T Takano","year":"1992","journal-title":"Human genetics"},{"issue":"3","key":"ref7","first-page":"108","article-title":"Pseudoeunuchoidism" in Recklinghausen's generalized neurofibromatosis]","volume":"17","author":"W. Meyhofer","year":"1966","journal-title":"Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete"},{"key":"ref8","first-page":"757","article-title":"Testicular Dystrophy in Recklinghausen's Neurofibromatosis]","volume":"41","author":"H Bricaire","year":"1965","journal-title":"La semaine des hopitaux: organe fonde par l'Association d'enseignement medical des hopitaux de Paris"},{"issue":"7","key":"ref9","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/ajmg.a.36001","article-title":"The generalized bone phenotype in children with neurofibromatosis 1: a sibling matched case-control study","volume":"161A","author":"L Armstrong","year":"2013","journal-title":"American journal of medical genetics Part A"},{"issue":"Suppl 2","key":"ref10","first-page":"289","article-title":"Growth and pubertal disorders in neurofibromatosis type 1","volume":"16","author":"R Virdis","year":"2003","journal-title":"Journal of pediatric endocrinology & metabolism: JPEM"},{"issue":"4","key":"ref11","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1136\/jmg.2008.061895","article-title":"Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1)","volume":"46","author":"T Tucker","year":"2009","journal-title":"Journal of medical genetics"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"849","DOI":"10.2147\/DDDT.S46101","article-title":"Causes, consequences, and treatment of osteoporosis in men","volume":"7","author":"J Banu","year":"2013","journal-title":"Drug design, development and therapy"},{"issue":"4\u20135","key":"ref13","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cytogfr.2005.05.007","article-title":"Cytokines and junction restructuring during spermatogenesis\u2014a lesson to learn from the testis","volume":"16","author":"W Xia","year":"2005","journal-title":"Cytokine & growth factor reviews"},{"issue":"1","key":"ref14","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/jcp.20377","article-title":"Disruption of Sertoli-germ cell adhesion function in the seminiferous epithelium of the rat testis can be limited to adherens junctions without affecting the blood-testis barrier integrity: an in vivo study using an androgen suppression model","volume":"205","author":"W Xia","year":"2005","journal-title":"Journal of cellular physiology"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1124\/pr.110.002790","article-title":"The blood-testis barrier and its implications for male contraception","volume":"64","author":"CY Cheng","year":"2012","journal-title":"Pharmacological reviews"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0070-2153(05)71008-5","article-title":"The blood-testis barrier: its biology, regulation, and physiological role in spermatogenesis","volume":"71","author":"CH Wong","year":"2005","journal-title":"Current topics in developmental biology"},{"issue":"Pt 5","key":"ref17","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1242\/jcs.00900","article-title":"Regulation of blood-testis barrier dynamics: an in vivo study","volume":"117","author":"CH Wong","year":"2004","journal-title":"Journal of cell science"},{"issue":"3","key":"ref18","first-page":"315","article-title":"Expression of the neurofibromatosis 1 (NF1) isoforms in developing and adult rat tissues","volume":"6","author":"DH Gutmann","year":"1995","journal-title":"Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1101\/SQB.1991.056.01.029","article-title":"Regulation of ras p21 by GTPase activating proteins","volume":"56","author":"F McCormick","year":"1991","journal-title":"Cold Spring Harbor symposia on quantitative biology"},{"issue":"21","key":"ref20","doi-asserted-by":"crossref","first-page":"14479","DOI":"10.1074\/jbc.M710492200","article-title":"Identification of Extracellular Signal-regulated Kinase 1\/2 and p38 MAPK as Regulators of Human Sperm Motility and Acrosome Reaction and as Predictors of Poor Spermatozoan Quality","volume":"283","author":"T Almog","year":"2008","journal-title":"Journal of Biological Chemistry"},{"issue":"1\u20132","key":"ref21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mce.2007.11.011","article-title":"Mitogen activated protein kinases (MAPKs) as regulators of spermatogenesis and spermatozoa functions","volume":"282","author":"T Almog","year":"2008","journal-title":"Molecular and cellular endocrinology"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1074\/jbc.M111.316372","article-title":"Long glucocorticoid-induced leucine zipper (L-GILZ) protein interacts with ras protein pathway and contributes to spermatogenesis control","volume":"287","author":"S Bruscoli","year":"2012","journal-title":"J Biol Chem"},{"issue":"11","key":"ref23","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1002\/stem.1486","article-title":"MEK\/ERK signaling directly and indirectly contributes to the cyclical self-renewal of spermatogonial stem cells","volume":"31","author":"K Hasegawa","year":"2013","journal-title":"Stem cells (Dayton, Ohio)"},{"issue":"2","key":"ref24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ydbio.2004.12.036","article-title":"TGF-beta3 regulates anchoring junction dynamics in the seminiferous epithelium of the rat testis via the Ras\/ERK signaling pathway: An in vivo study","volume":"280","author":"W Xia","year":"2005","journal-title":"Developmental biology"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2005.08.001","article-title":"Mitogen-activated protein kinases, adherens junction dynamics, and spermatogenesis: a review of recent data","volume":"286","author":"CH Wong","year":"2005","journal-title":"Developmental biology"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1634\/stemcells.2007-0436","article-title":"Gdnf upregulates c-Fos transcription via the Ras\/Erk1\/2 pathway to promote mouse spermatogonial stem cell proliferation","volume":"26","author":"Z He","year":"2008","journal-title":"Stem cells (Dayton, Ohio)"},{"issue":"1","key":"ref27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.stem.2009.04.020","article-title":"Genetic reconstruction of mouse spermatogonial stem cell self-renewal in vitro by Ras-cyclin D2 activation","volume":"5","author":"J Lee","year":"2009","journal-title":"Cell stem cell"},{"issue":"6","key":"ref28","doi-asserted-by":"crossref","first-page":"12345","DOI":"10.3390\/ijms160612345","article-title":"Hyperactive RAS\/PI3-K\/MAPK Signaling Cascade in Migration and Adhesion of Nf1 Haploinsufficient Mesenchymal Stem\/Progenitor Cells","volume":"16","author":"Y Zhou","year":"2015","journal-title":"International journal of molecular sciences"},{"issue":"1","key":"ref29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/jid.2012.240","article-title":"Differential effects of neurofibromin gene dosage on melanocyte development","volume":"133","author":"M Deo","year":"2013","journal-title":"The Journal of investigative dermatology"},{"issue":"6","key":"ref30","doi-asserted-by":"crossref","first-page":"685","DOI":"10.2164\/jandrol.108.006460","article-title":"Measurement of testicular volume in smaller testes: how accurate is the conventional orchidometer?","volume":"30","author":"CC Lin","year":"2009","journal-title":"Journal of andrology"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.mce.2009.05.009","article-title":"The role of Mitogen activated protein kinase (MAPK) in sperm functions","volume":"314","author":"T Almog","year":"2010","journal-title":"Molecular and cellular endocrinology"},{"issue":"6","key":"ref32","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/j.1939-4640.2001.tb03444.x","article-title":"Structure and control of a cell-cell adhesion complex associated with spermiation in rat seminiferous epithelium","volume":"22","author":"RE Chapin","year":"2001","journal-title":"Journal of andrology"},{"issue":"6","key":"ref33","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1096\/fj.06-070342","article-title":"Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells","volume":"22","author":"HH Yan","year":"2008","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"3","key":"ref34","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1095\/biolreprod.105.040766","article-title":"Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)\/cGMP\/protein kinase G (PRKG)\/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study","volume":"73","author":"NP Lee","year":"2005","journal-title":"Biology of reproduction"},{"issue":"4","key":"ref35","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1210\/en.2002-0211","article-title":"TGF-beta3 regulates the blood-testis barrier dynamics via the p38 mitogen activated protein (MAP) kinase pathway: an in vivo study","volume":"144","author":"WY Lui","year":"2003","journal-title":"Endocrinology"},{"issue":"33","key":"ref36","doi-asserted-by":"crossref","first-page":"11722","DOI":"10.1073\/pnas.0503855102","article-title":"Blood-testis barrier dynamics are regulated by an engagement\/disengagement mechanism between tight and adherens junctions via peripheral adaptors","volume":"102","author":"HH Yan","year":"2005","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1095\/biolreprod63.1.99","article-title":"Sertoli cell ectoplasmic specializations in the seminiferous epithelium of the testosterone-suppressed adult rat","volume":"63","author":"L O'Donnell","year":"2000","journal-title":"Biology of reproduction"},{"issue":"3","key":"ref38","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2164\/jandrol.04149","article-title":"Regulatory cytokine expression and interstitial fluid formation in the normal and inflamed rat testis are under leydig cell control","volume":"26","author":"M Hedger","year":"2005","journal-title":"Journal of andrology"},{"issue":"4","key":"ref39","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1095\/biolreprod55.4.895","article-title":"Testosterone withdrawal promotes stage-specific detachment of round spermatids from the rat seminiferous epithelium","volume":"55","author":"L O'Donnell","year":"1996","journal-title":"Biology of reproduction"},{"issue":"1","key":"ref40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4161\/spmg.1.1.14525","article-title":"Spermiation: The process of sperm release","volume":"1","author":"L O'Donnell","year":"2011","journal-title":"Spermatogenesis"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ydbio.2007.10.013","article-title":"JAM-A is present in mammalian spermatozoa where it is essential for normal motility","volume":"313","author":"M Shao","year":"2008","journal-title":"Developmental biology"},{"issue":"10","key":"ref42","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/mrd.22528","article-title":"Lack of protein kinase C-delta (PKCdelta) disrupts fertilization and embryonic development","volume":"82","author":"W Ma","year":"2015","journal-title":"Molecular reproduction and development"},{"issue":"10","key":"ref43","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1210\/en.2005-0490","article-title":"Enhanced sexual behaviors and androgen receptor immunoreactivity in the male progesterone receptor knockout mouse","volume":"146","author":"JS Schneider","year":"2005","journal-title":"Endocrinology"},{"issue":"2","key":"ref44","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.2047-2927.2012.00047.x","article-title":"Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents","volume":"1","author":"Y Lue","year":"2013","journal-title":"Andrology"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1095\/biolreprod67.4.1327","article-title":"Progesterone receptor as an indicator of sperm function","volume":"67","author":"S Gadkar","year":"2002","journal-title":"Biology of reproduction"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0090-4295(98)00438-5","article-title":"Testicular microlithiasis is associated with testicular pathology","volume":"53","author":"JP Ganem","year":"1999","journal-title":"Urology"},{"issue":"9253","key":"ref47","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0140-6736(05)71531-2","article-title":"Bilateral testicular tumour in neurofibromatosis type 1","volume":"357","author":"H Kume","year":"2001","journal-title":"Lancet (London, England)"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/pbc.22297","article-title":"Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia","volume":"54","author":"M Raygada","year":"2010","journal-title":"Pediatric blood & cancer"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0208835","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T19:14:12Z","timestamp":1588965252000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0208835"}},"subtitle":[],"editor":[{"given":"Stefan","family":"Schlatt","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,12,20]]},"references-count":48,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0208835","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,20]]}}}