{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T21:57:35Z","timestamp":1755035855685,"version":"3.41.2"},"reference-count":22,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000016","name":"DHHS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"publisher","award":["1F32-DE021307"],"award-info":[{"award-number":["1F32-DE021307"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Murray-Heilig Fund in Molecular Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hyperparathyroidism jaw-tumor syndrome is an autosomal dominant disorder caused by mutations in the CDC73\/HRPT2 tumor suppressor gene, encoding parafibromin, and manifesting benign or malignant parathyroid tumors, ossifying jaw fibromas, uterine tumors, and kidney lesions. Sporadic parathyroid carcinomas also frequently exhibit inactivating CDC73 mutations and loss of parafibromin. To study the role of CDC73 in parathyroid cell proliferation in vivo, we generated mice with a parathyroid-specific deletion of Cdc73. Homozygous knockout mice on a mixed B6\/129\/CD1 background had decreased serum calcium and PTH and smaller parathyroid glands compared with heterozygous or wild-type littermates, whereas homozygous Cdc73-null mice on other backgrounds exhibited no abnormalities in parathyroid gland function or development. No hypercalcemia or parathyroid hypercellularity was observed in mice of any background examined at any age. Thus, although postnatally acquired complete loss of CDC73 causes parathyroid cell proliferation and hyperparathyroidism, such as seen in human hyperparathyroidism jaw-tumor syndrome, our results suggest that earlier, developmentally imposed complete loss of Cdc73 can cause a primary defect in parathyroid gland structure\/function in a strain-dependent manner. This striking disparity in parathyroid phenotype related to genetic background offers a unique opportunity in an in vivo model system to precisely dissect and identify the responsible molecular mechanisms.<\/jats:p>","DOI":"10.1210\/jendso\/bvae006","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T20:38:12Z","timestamp":1705783092000},"source":"Crossref","is-referenced-by-count":1,"title":["Phenotype of Parathyroid-targeted <i>Cdc73<\/i> Deletion in Mice Is Strain-dependent"],"prefix":"10.1210","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-1693","authenticated-orcid":false,"given":"Jessica","family":"Costa-Guda","sequence":"first","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"},{"name":"Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut School of Dental Medicine, Farmington, CT 06030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah T","family":"Cohen","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Romano","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Acostamadiedo","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"},{"name":"Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Clark","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"},{"name":"Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Bellizzi","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Arnold","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"},{"name":"Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington, CT 06030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"issue":"4","key":"2024020719251652100_bvae006-B1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/ng1048","article-title":"HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome","volume":"32","author":"Carpten","year":"2002","journal-title":"Nat Genet"},{"issue":"1","key":"2024020719251652100_bvae006-B2","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1210\/jc.2003-030675","article-title":"Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome","volume":"89","author":"Simonds","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2024020719251652100_bvae006-B3","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1136\/jmg.2003.012369","article-title":"Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP)","volume":"41","author":"Villablanca","year":"2004","journal-title":"J Med Genet"},{"issue":"18","key":"2024020719251652100_bvae006-B4","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1056\/NEJMoa031237","article-title":"Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma","volume":"349","author":"Shattuck","year":"2003","journal-title":"N Engl J Med"},{"issue":"9","key":"2024020719251652100_bvae006-B5","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1136\/jmg.40.9.657","article-title":"HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours","volume":"40","author":"Howell","year":"2003","journal-title":"J Med Genet"},{"issue":"11","key":"2024020719251652100_bvae006-B6","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1210\/jc.2004-0294","article-title":"Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors","volume":"89","author":"Cetani","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2024020719251652100_bvae006-B7","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/j.1365-2265.2007.02894.x","article-title":"Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas","volume":"67","author":"Haven","year":"2007","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"6","key":"2024020719251652100_bvae006-B8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s13402-012-0100-x","article-title":"CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort","volume":"35","author":"Guarnieri","year":"2012","journal-title":"Cell Oncol (Dordr)"},{"issue":"23","key":"2024020719251652100_bvae006-B9","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1038\/sj.onc.1210131","article-title":"Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene","volume":"26","author":"Zhao","year":"2007","journal-title":"Oncogene"},{"issue":"7","key":"2024020719251652100_bvae006-B10","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.oraloncology.2005.11.019","article-title":"HRPT2 gene alterations in ossifying fibroma of the jaws","volume":"42","author":"Pimenta","year":"2006","journal-title":"Oral Oncol"},{"issue":"2","key":"2024020719251652100_bvae006-B11","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.cell.2006.01.053","article-title":"Parafibromin\/Hyrax activates Wnt\/Wg target gene transcription by direct association with beta-catenin\/Armadillo","volume":"125","author":"Mosimann","year":"2006","journal-title":"Cell"},{"issue":"12","key":"2024020719251652100_bvae006-B12","doi-asserted-by":"crossref","first-page":"5052","DOI":"10.1128\/MCB.25.12.5052-5060.2005","article-title":"The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II","volume":"25","author":"Yart","year":"2005","journal-title":"Mol Cell Biol"},{"issue":"1","key":"2024020719251652100_bvae006-B13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bbrc.2006.08.169","article-title":"Parafibromin inhibits cancer cell growth and causes G1 phase arrest","volume":"350","author":"Zhang","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"issue":"7","key":"2024020719251652100_bvae006-B14","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/sj.onc.1208274","article-title":"Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1\/PRAD1 expression","volume":"24","author":"Woodard","year":"2005","journal-title":"Oncogene"},{"issue":"9","key":"2024020719251652100_bvae006-B15","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1128\/MCB.00654-07","article-title":"Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice","volume":"28","author":"Wang","year":"2008","journal-title":"Mol Cell Biol"},{"issue":"28","key":"2024020719251652100_bvae006-B16","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1038\/onc.2017.43","article-title":"Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: model for the hyperparathyroidism-jaw tumour syndrome","volume":"36","author":"Walls","year":"2017","journal-title":"Oncogene"},{"issue":"22","key":"2024020719251652100_bvae006-B17","first-page":"8022","article-title":"Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid neoplasia and hypercalcemic hyperparathyroidism","volume":"63","author":"Libutti","year":"2003","journal-title":"Cancer Res"},{"issue":"9","key":"2024020719251652100_bvae006-B18","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1172\/JCI10523","article-title":"Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice","volume":"107","author":"Imanishi","year":"2001","journal-title":"J Clin Invest"},{"issue":"24","key":"2024020719251652100_bvae006-B19","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1101\/gad.8.24.2964","article-title":"Colorectal hyperplasia and inflammation in keratin 8-deficient FVB\/N mice","volume":"8","author":"Baribault","year":"1994","journal-title":"Genes Dev"},{"key":"2024020719251652100_bvae006-B20","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/978-1-59745-471-1_23","article-title":"Influence of genetic background on genetically engineered mouse phenotypes","volume":"530","author":"Doetschman","year":"2009","journal-title":"Methods Mol Biol"},{"issue":"1","key":"2024020719251652100_bvae006-B21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1242\/dmm.009795","article-title":"Learning from a paradox: recent insights into Fanconi anaemia through studying mouse models","volume":"6","author":"Bakker","year":"2013","journal-title":"Dis Model Mech"},{"issue":"1","key":"2024020719251652100_bvae006-B22","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.kint.2022.03.020","article-title":"The impact of genetic background on mouse models of kidney disease","volume":"102","author":"Bufi","year":"2022","journal-title":"Kidney Int"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/jendso\/bvae006\/56278598\/bvae006.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/8\/3\/bvae006\/56615210\/bvae006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/8\/3\/bvae006\/56615210\/bvae006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T19:26:03Z","timestamp":1707333963000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/doi\/10.1210\/jendso\/bvae006\/7581885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,1,16]]}},"URL":"https:\/\/doi.org\/10.1210\/jendso\/bvae006","relation":{},"ISSN":["2472-1972"],"issn-type":[{"type":"electronic","value":"2472-1972"}],"subject":[],"published-other":{"date-parts":[[2024,3]]},"published":{"date-parts":[[2024,1,16]]},"article-number":"bvae006"}}