{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:14:34Z","timestamp":1787022874184,"version":"build-2736575974"},"reference-count":38,"publisher":"Japanese Association for Laboratory Animal Science","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp. Anim."],"published-print":{"date-parts":[[2018]]},"DOI":"10.1538\/expanim.17-0060","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T18:08:37Z","timestamp":1503598117000},"page":"63-70","source":"Crossref","is-referenced-by-count":21,"title":["Progranulin haploinsufficiency reduces amyloid beta deposition in Alzheimer\u2019s disease model mice"],"prefix":"10.1538","volume":"67","author":[{"given":"Masato","family":"Hosokawa","sequence":"first","affiliation":[{"name":"Dementia research project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Dementia research project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuaki","family":"Arai","sequence":"additional","affiliation":[{"name":"Dementia research project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan"},{"name":"Department of Neuropsychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8576 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Histology center, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Dementia research project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Dementia research project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"439","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Baker M., Mackenzie I.R., Pickering-Brown S.M., Gass J., Rademakers R., Lindholm C., Snowden J., Adamson J., Sadovnick A.D., Rollinson S., Cannon A., Dwosh E., Neary D., Melquist S., Richardson A., Dickson D., Berger Z., Eriksen J., Robinson T., Zehr C., Dickey C.A., Crook R., McGowan E., Mann D., Boeve B., Feldman H., and Hutton M. 2006. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. <i>Nature<\/i> 442: 916\u2013919.","DOI":"10.1038\/nature05016"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Benussi L., Binetti G., Sina E., Gigola L., Bettecken T., Meitinger T., and Ghidoni R. 2008. A novel deletion in progranulin gene is associated with FTDP-17 and CBS. <i>Neurobiol. Aging<\/i> 29: 427\u2013435.","DOI":"10.1016\/j.neurobiolaging.2006.10.028"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Brouwers N., Nuytemans K., van der Zee J., Gijselinck I., Engelborghs S., Theuns J., Kumar-Singh S., Pickut B.A., Pals P., Dermaut B., Bogaerts V., De Pooter T., Serneels S., Van den Broeck M., Cuijt I., Mattheijssens M., Peeters K., Sciot R., Martin J.J., Cras P., Santens P., Vandenberghe R., De Deyn P.P., Cruts M., Van Broeckhoven C., and Sleegers K. 2007. Alzheimer and Parkinson diagnoses in progranulin null mutation carriers in an extended founder family. <i>Arch. Neurol.<\/i> 64: 1436\u20131446.","DOI":"10.1001\/archneur.64.10.1436"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Brouwers N., Sleegers K., Engelborghs S., Maurer-Stroh S., Gijselinck I., van der Zee J., Pickut B.A., Van den Broeck M., Mattheijssens M., Peeters K., Schymkowitz J., Rousseau F., Martin J.J., Cruts M., De Deyn P.P., and Van Broeckhoven C. 2008. Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease. <i>Neurology<\/i> 71: 656\u2013664.","DOI":"10.1212\/01.wnl.0000319688.89790.7a"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Carecchio M., Fenoglio C., De Riz M., Guidi I., Comi C., Cortini F., Venturelli E., Restelli I., Cantoni C., Bresolin N., Monaco F., Scarpini E., and Galimberti D. 2009. Progranulin plasma levels as potential biomarker for the identification of GRN deletion carriers. A case with atypical onset as clinical amnestic Mild Cognitive Impairment converted to Alzheimer\u2019s disease. <i>J. Neurol. Sci.<\/i> 287: 291\u2013293.","DOI":"10.1016\/j.jns.2009.07.011"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Cortini F., Fenoglio C., Guidi I., Venturelli E., Pomati S., Marcone A., Scalabrini D., Villa C., Clerici F., Dalla Valle E., Mariani C., Cappa S., Bresolin N., Scarpini E., and Galimberti D. 2008. Novel exon 1 progranulin gene variant in Alzheimer\u2019s disease. <i>Eur. J. Neurol.<\/i> 15: 1111\u20131117.","DOI":"10.1111\/j.1468-1331.2008.02266.x"},{"key":"7","unstructured":"7. Daniel R., Daniels E., He Z., and Bateman A. 2003. Progranulin (acrogranin\/PC cell-derived growth factor\/granulin-epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development. <i>Dev. Dyn.<\/i> 227: 593\u2013599."},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Fenoglio C., Galimberti D., Cortini F., Kauwe J.S., Cruchaga C., Venturelli E., Villa C., Serpente M., Scalabrini D., Mayo K., Piccio L.M., Clerici F., Albani D., Mariani C., Forloni G., Bresolin N., Goate A.M., and Scarpini E. 2009. Rs5848 variant influences GRN mRNA levels in brain and peripheral mononuclear cells in patients with Alzheimer\u2019s disease. <i>J. Alzheimers Dis.<\/i> 18: 603\u2013612.","DOI":"10.3233\/JAD-2009-1170"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Finch N., Baker M., Crook R., Swanson K., Kuntz K., Surtees R., Bisceglio G., Rovelet-Lecrux A., Boeve B., Petersen R.C., Dickson D.W., Younkin S.G., Deramecourt V., Crook J., Graff-Radford N.R., and Rademakers R. 2009. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. <i>Brain<\/i> 132: 583\u2013591.","DOI":"10.1093\/brain\/awn352"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Greenberg S.G. and Davies P. 1990. A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. <i>Proc. Natl. Acad. Sci. USA<\/i> 87: 5827\u20135831.","DOI":"10.1073\/pnas.87.15.5827"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. He Z., Ong C.H., Halper J., and Bateman A. 2003. Progranulin is a mediator of the wound response. <i>Nat. Med.<\/i> 9: 225\u2013229.","DOI":"10.1038\/nm816"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Hosokawa M., Arai T., Masuda-Suzukake M., Kondo H., Matsuwaki T., Nishihara M., Hasegawa M., and Akiyama H. 2015. Progranulin reduction is associated with increased tau phosphorylation in P301L tau transgenic mice. <i>J. Neuropathol. Exp. Neurol.<\/i> 74: 158\u2013165.","DOI":"10.1097\/NEN.0000000000000158"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Hosokawa M., Arai T., Masuda-Suzukake M., Nonaka T., Yamashita M., Akiyama H., and Hasegawa M. 2012. Methylene blue reduced abnormal tau accumulation in P301L tau transgenic mice. <i>PLoS One<\/i> 7: e52389.","DOI":"10.1371\/journal.pone.0052389"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Hosokawa M., Kondo H., Serrano G.E., Beach T.G., Robinson A.C., Mann D.M., Akiyama H., Hasegawa M., and Arai T. 2017. Accumulation of multiple neurodegenerative disease-related proteins in familial frontotemporal lobar degeneration associated with granulin mutation. <i>Sci. Rep.<\/i> 7: 1513.","DOI":"10.1038\/s41598-017-01587-6"},{"key":"15","unstructured":"15. Hsiao K., Chapman P., Nilsen S., Eckman C., Harigaya Y., Younkin S., Yang F., and Cole G. 1996. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. <i>Science<\/i> 274: 99\u2013102."},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Josephs K.A., Ahmed Z., Katsuse O., Parisi J.F., Boeve B.F., Knopman D.S., Petersen R.C., Davies P., Duara R., Graff-Radford N.R., Uitti R.J., Rademakers R., Adamson J., Baker M., Hutton M.L., and Dickson D.W. 2007. Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions with progranulin gene (PGRN) mutations. <i>J. Neuropathol. Exp. Neurol.<\/i> 66: 142\u2013151.","DOI":"10.1097\/nen.0b013e31803020cf"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Kayasuga Y., Chiba S., Suzuki M., Kikusui T., Matsuwaki T., Yamanouchi K., Kotaki H., Horai R., Iwakura Y., and Nishihara M. 2007. Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene. <i>Behav. Brain Res.<\/i> 185: 110\u2013118.","DOI":"10.1016\/j.bbr.2007.07.020"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Kelley B.J., Haidar W., Boeve B.F., Baker M., Graff-Radford N.R., Krefft T., Frank A.R., Jack C.R. Jr., Shiung M., Knopman D.S., Josephs K.A., Parashos S.A., Rademakers R., Hutton M., Pickering-Brown S., Adamson J., Kuntz K.M., Dickson D.W., Parisi J.E., Smith G.E., Ivnik R.J., and Petersen R.C. 2009. Prominent phenotypic variability associated with mutations in Progranulin. <i>Neurobiol. Aging<\/i> 30: 739\u2013751.","DOI":"10.1016\/j.neurobiolaging.2007.08.022"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Kelley B.J., Haidar W., Boeve B.F., Baker M., Shiung M., Knopman D.S., Rademakers R., Hutton M., Adamson J., Kuntz K.M., Dickson D.W., Parisi J.E., Smith G.E., and Petersen R.C. 2010. Alzheimer disease-like phenotype associated with the c.154delA mutation in progranulin. <i>Arch. Neurol.<\/i> 67: 171\u2013177.","DOI":"10.1001\/archneurol.2010.113"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Le Ber I., Camuzat A., Hannequin D., Pasquier F., Guedj E., Rovelet-Lecrux A., Hahn-Barma V., van der Zee J., Clot F., Bakchine S., Puel M., Ghanim M., Lacomblez L., Mikol J., Deramecourt V., Lejeune P., de la Sayette V., Belliard S., Vercelletto M., Meyrignac C., Van Broeckhoven C., Lambert J.C., Verpillat P., Campion D., Habert M.O., Dubois B., Brice A., French research network on FTD\/FTD-MND 2008. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study. <i>Brain<\/i> 131: 732\u2013746.","DOI":"10.1093\/brain\/awn012"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Lee M.J., Chen T.F., Cheng T.W., and Chiu M.J. 2011. rs5848 variant of progranulin gene is a risk of Alzheimer\u2019s disease in the Taiwanese population. <i>Neurodegener. Dis.<\/i> 8: 216\u2013220.","DOI":"10.1159\/000322538"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Lui H., Zhang J., Makinson S.R., Cahill M.K., Kelley K.W., Huang H.Y., Shang Y., Oldham M.C., Martens L.H., Gao F., Coppola G., Sloan S.A., Hsieh C.L., Kim C.C., Bigio E.H., Weintraub S., Mesulam M.M., Rademakers R., Mackenzie I.R., Seeley W.W., Karydas A., Miller B.L., Borroni B., Ghidoni R., Farese R.V. Jr., Paz J.T., Barres B.A., and Huang E.J. 2016. Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. <i>Cell<\/i> 165: 921\u2013935.","DOI":"10.1016\/j.cell.2016.04.001"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Masellis M., Momeni P., Meschino W., Heffner R. Jr., Elder J., Sato C., Liang Y., St George-Hyslop P., Hardy J., Bilbao J., Black S., and Rogaeva E. 2006. Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome. <i>Brain<\/i> 129: 3115\u20133123.","DOI":"10.1093\/brain\/awl276"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Minami S.S., Min S.W., Krabbe G., Wang C., Zhou Y., Asgarov R., Li Y., Martens L.H., Elia L.P., Ward M.E., Mucke L., Farese R.V. Jr., and Gan L. 2014. Progranulin protects against amyloid \u03b2 deposition and toxicity in Alzheimer\u2019s disease mouse models. <i>Nat. Med.<\/i> 20: 1157\u20131164.","DOI":"10.1038\/nm.3672"},{"key":"25","unstructured":"25. Mukherjee O., Pastor P., Cairns N.J., Chakraverty S., Kauwe J.S., Shears S., Behrens M.I., Budde J., Hinrichs A.L., Norton J., Levitch D., Taylor-Reinwald L., Gitcho M., Tu P.H., Tenenholz Grinberg L., Liscic R.M., Armendariz J., Morris J.C., and Goate A.M. 2006. HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin. <i>Ann. Neurol.<\/i> 60: 314\u2013322."},{"key":"26","unstructured":"26. Ong C.H. and Bateman A. 2003. Progranulin (granulin-epithelin precursor, PC-cell derived growth factor, acrogranin) in proliferation and tumorigenesis. <i>Histol. Histopathol.<\/i> 18: 1275\u20131288."},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Perry D.C., Lehmann M., Yokoyama J.S., Karydas A., Lee J.J., Coppola G., Grinberg L.T., Geschwind D., Seeley W.W., Miller B.L., Rosen H., and Rabinovici G. 2013. Progranulin mutations as risk factors for Alzheimer disease. <i>JAMA Neurol.<\/i> 70: 774\u2013778.","DOI":"10.1001\/2013.jamaneurol.393"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Pickford F., Marcus J., Camargo L.M., Xiao Q., Graham D., Mo J.R., Burkhardt M., Kulkarni V., Crispino J., Hering H., and Hutton M. 2011. Progranulin is a chemoattractant for microglia and stimulates their endocytic activity. <i>Am. J. Pathol.<\/i> 178: 284\u2013295.","DOI":"10.1016\/j.ajpath.2010.11.002"},{"key":"29","unstructured":"29. Rosen E.Y., Wexler E.M., Versano R., Coppola G., Gao F., Winden K.D., Oldham M.C., Martens L.H., Zhou P., Farese R.V. Jr., and Geschwind D.H. 2011. Functional genomic analyses identify pathways dysregulated by progranulin deficiency, implicating Wnt signaling. <i>Neuron<\/i> 71: 1030\u20131042."},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Sleegers K., Brouwers N., Van Damme P., Engelborghs S., Gijselinck I., van der Zee J., Peeters K., Mattheijssens M., Cruts M., Vandenberghe R., De Deyn P.P., Robberecht W., and Van Broeckhoven C. 2009. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. <i>Ann. Neurol.<\/i> 65: 603\u2013609.","DOI":"10.1002\/ana.21621"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Spina S., Murrell J.R., Huey E.D., Wassermann E.M., Pietrini P., Grafman J., and Ghetti B. 2007. Corticobasal syndrome associated with the A9D Progranulin mutation. <i>J. Neuropathol. Exp. Neurol.<\/i> 66: 892\u2013900.","DOI":"10.1097\/nen.0b013e3181567873"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Takahashi H., Klein Z.A., Bhagat S.M., Kaufman A.C., Kostylev M.A., Ikezu T., Strittmatter S.M., Alzheimer\u2019s Disease Neuroimaging Initiative. 2017. Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. <i>Acta Neuropathol.<\/i> 133: 785\u2013807.","DOI":"10.1007\/s00401-017-1668-z"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Tanaka Y., Chambers J.K., Matsuwaki T., Yamanouchi K., and Nishihara M. 2014. Possible involvement of lysosomal dysfunction in pathological changes of the brain in aged progranulin-deficient mice. <i>Acta Neuropathol. Commun.<\/i> 2: 78.","DOI":"10.1186\/PREACCEPT-4589926441299369"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Tanaka Y., Matsuwaki T., Yamanouchi K., and Nishihara M. 2013. Increased lysosomal biogenesis in activated microglia and exacerbated neuronal damage after traumatic brain injury in progranulin-deficient mice. <i>Neuroscience<\/i> 250: 8\u201319.","DOI":"10.1016\/j.neuroscience.2013.06.049"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Tanaka Y., Suzuki G., Matsuwaki T., Hosokawa M., Serrano G., Beach T.G., Yamanouchi K., Hasegawa M., and Nishihara M. 2017. Progranulin regulates lysosomal function and biogenesis through acidification of lysosomes. <i>Hum. Mol. Genet.<\/i> 26: 969\u2013988.","DOI":"10.1093\/hmg\/ddx011"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Van Damme P., Van Hoecke A., Lambrechts D., Vanacker P., Bogaert E., van Swieten J., Carmeliet P., Van Den Bosch L., and Robberecht W. 2008. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. <i>J. Cell Biol.<\/i> 181: 37\u201341.","DOI":"10.1083\/jcb.200712039"},{"key":"37","unstructured":"37. Yin F., Banerjee R., Thomas B., Zhou P., Qian L., Jia T., Ma X., Ma Y., Iadecola C., Beal M.F., Nathan C., and Ding A. 2010. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. <i>J. Exp. Med.<\/i> 207: 117\u2013128."},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Zhu J., Nathan C., Jin W., Sim D., Ashcroft G.S., Wahl S.M., Lacomis L., Erdjument-Bromage H., Tempst P., Wright C.D., and Ding A. 2002. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. <i>Cell<\/i> 111: 867\u2013878.","DOI":"10.1016\/S0092-8674(02)01141-8"}],"container-title":["Experimental Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/expanim\/67\/1\/67_17-0060\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T15:53:03Z","timestamp":1570031583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/expanim\/67\/1\/67_17-0060\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1538\/expanim.17-0060","relation":{},"ISSN":["1341-1357","1881-7122"],"issn-type":[{"value":"1341-1357","type":"print"},{"value":"1881-7122","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018]]}}}