{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:31:34Z","timestamp":1777555894438,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p> UDP-GlcNAc: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) is an \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub> hexameric enzyme that catalyzes the first step in the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. In humans, mutations in the gene encoding the \u03b1\/\u03b2 subunit precursor give rise to mucolipidosis II (MLII), whereas mutations in the gene encoding the \u03b3 subunit cause the less severe mucolipidosis IIIC (MLIIIC). In this study we describe the phenotypic, histologic, and serum lysosomal enzyme abnormalities in knockout mice lacking the \u03b3 subunit and compare these findings to those of mice lacking the \u03b1\/\u03b2 subunits and humans with MLII and MLIIIC. We found that both lines of mutant mice had elevated levels of serum lysosomal enzymes and cytoplasmic alterations in secretory cells of several exocrine glands; however, lesions in \u03b3-subunit deficient ( Gnptab<jats:sup>-\/-<\/jats:sup>) mice were milder and more restricted in distribution than in \u03b1\/\u03b2-subunit deficient ( Gnptab<jats:sup>-\/-<\/jats:sup>) mice. We found that onset, extent, and severity of lesions that developed in these two different knockouts correlated with measured lysosomal enzyme activity; with a more rapid, widespread, and severe storage disease phenotype developing in Gnptab<jats:sup>-\/-<\/jats:sup> mice. In contrast to mice deficient in the \u03b1\/\u03b2 subunits, the mice lacking the \u03b3 subunits were of normal size, lacked cartilage defects, and did not develop retinal degeneration. The milder disease in the \u03b3-subunit deficient mice correlated with residual synthesis of the mannose 6-phosphate recognition marker. Of significance, neither strain of mutant mice developed cytoplasmic vacuolar inclusions in fibrocytes or mesenchymal cells (I-cells), the characteristic lesion associated with the prominent skeletal and connective tissue abnormalities in humans with MLII and MLIII. Instead, the predominant lesions in both lines of mice were found in the secretory epithelial cells of several exocrine glands, including the pancreas, and the parotid, submandibular salivary, nasal, lacrimal, bulbourethral, and gastric glands. The absence of retinal and chondrocyte lesions in Gnptab<jats:sup>-\/-<\/jats:sup> mice might be attributed to residual \u03b2-glucuronidase activity. We conclude that mice lacking either \u03b1\/\u03b2 or \u03b3 subunits displayed clinical and pathologic features that differed substantially from those reported in humans having mutations in orthologous genes. <\/jats:p>","DOI":"10.1354\/vp.46-2-313","type":"journal-article","created":{"date-parts":[[2009,3,4]],"date-time":"2009-03-04T09:03:55Z","timestamp":1236157435000},"page":"313-324","source":"Crossref","is-referenced-by-count":40,"title":["Comparative Pathology of Murine Mucolipidosis Types II and                IIIC"],"prefix":"10.1177","volume":"46","author":[{"given":"P.","family":"Vogel","sequence":"first","affiliation":[{"name":"Lexicon Pharmaceuticals, Inc., The Woodlands, TX;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. J.","family":"Payne","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Inc., The Woodlands, TX;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Read","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Inc., The Woodlands, TX;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.-S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Washington University School of\r            Medicine, St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. M.","family":"Gelfman","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Inc., The Woodlands, TX;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Kornfeld","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Washington University School of\r            Medicine, St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2009,3,1]]},"reference":[{"key":"bibr1-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(89)80027-2"},{"key":"bibr2-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1042\/bj3320593"},{"key":"bibr3-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.49.31446"},{"key":"bibr4-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.03.003"},{"key":"bibr5-vp.46-2-313","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/0470014067.ch10","volume-title":"Model Organisms in Drug Discovery","author":"Beltrandelrio H","year":"2003"},{"key":"bibr6-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2829"},{"key":"bibr7-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114010"},{"key":"bibr8-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1177\/030098589603300101"},{"key":"bibr9-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008823315416"},{"key":"bibr10-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.10.1591"},{"key":"bibr11-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202369200"},{"key":"bibr12-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0483-4"},{"key":"bibr13-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050292"},{"key":"bibr14-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.3.775"},{"key":"bibr15-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0452"},{"key":"bibr16-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1050"},{"key":"bibr17-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.123.1.99"},{"key":"bibr18-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a131034"},{"key":"bibr19-vp.46-2-313","first-page":"415","volume":"60","author":"Hirano T","year":"1991","journal-title":"Nippon Geka Hokan"},{"key":"bibr20-vp.46-2-313","volume-title":"Guide for the care and use of laboratory animals","author":"Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council","year":"1996"},{"key":"bibr21-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.5.2026"},{"key":"bibr22-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.2.359"},{"key":"bibr23-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00035-6"},{"key":"bibr24-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112262"},{"key":"bibr25-vp.46-2-313","first-page":"3469","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Kornfeld S","year":"2000"},{"key":"bibr26-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509008200"},{"key":"bibr27-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1086\/500849"},{"key":"bibr28-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.3.595"},{"key":"bibr29-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1993.1067"},{"key":"bibr30-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704067200"},{"key":"bibr31-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197009102831117"},{"key":"bibr32-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/esg080"},{"key":"bibr33-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(82)91042-7"},{"key":"bibr34-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20205"},{"key":"bibr35-vp.46-2-313","doi-asserted-by":"crossref","unstructured":"35 Pazzaglia UE, Beluffi G, Castello A, Coci A, Zatti G: Bone changes of mucolipidosis II at different ages:                   postmortem study of three cases. Clin Orthop Relat Res:                   283\u2013290, 1992","DOI":"10.1097\/00003086-199203000-00040"},{"key":"bibr36-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.015222"},{"key":"bibr37-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5826"},{"key":"bibr38-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1999.0700"},{"key":"bibr39-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64427-6"},{"key":"bibr40-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81192-7"},{"key":"bibr41-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.12.015"},{"key":"bibr42-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(90)90041-R"},{"key":"bibr43-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1038\/nm1305"},{"key":"bibr44-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(88)90181-7"},{"key":"bibr45-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.12.7773"},{"key":"bibr46-vp.46-2-313","first-page":"717","volume":"34","author":"Varki A","year":"1982","journal-title":"Am J Hum Genet"},{"key":"bibr47-vp.46-2-313","first-page":"1217","volume":"31","author":"Yamada T","year":"1990","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bibr48-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2336103100"},{"key":"bibr49-vp.46-2-313","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1510"}],"container-title":["Veterinary Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1354\/vp.46-2-313","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1354\/vp.46-2-313","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1354\/vp.46-2-313","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T19:02:54Z","timestamp":1741114974000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1354\/vp.46-2-313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["10.1354\/vp.46-2-313"],"URL":"https:\/\/doi.org\/10.1354\/vp.46-2-313","relation":{},"ISSN":["0300-9858","1544-2217"],"issn-type":[{"value":"0300-9858","type":"print"},{"value":"1544-2217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3]]}}}