{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:08:55Z","timestamp":1791857335491,"version":"4.3.4"},"reference-count":45,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK11794"],"award-info":[{"award-number":["DK11794"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK113039"],"award-info":[{"award-number":["DK113039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR066261"],"award-info":[{"award-number":["AR066261"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward diseases of bone and mineral ion metabolism. Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs are 91% identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based assays in vitro. This introduces an element of uncertainty in the accuracy of rodent models for performing such preclinical evaluations. To overcome this potential uncertainty, we used a homologous recombination-based knockin (KI) approach to generate a mouse (in-host strain C57Bl\/6N) in which complementary DNA encoding the human PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R protein is expressed. Expression is directed by the endogenous mouse promoter and hence occurs in all biologically relevant cells and tissues and at appropriate levels. The resulting homozygous hPTH1R-KI (humanized) mice were healthy over at least 10 generations and showed functional responses to injected PTH analog peptides that are consistent with a fully functional human PTH1R in target bone and kidney cells. The initial evaluation of these mice and their potential utility for predicting behavior of PTH analogues in humans is reported here.<\/jats:p>","DOI":"10.1210\/endocr\/bqac054","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T13:18:03Z","timestamp":1650719883000},"source":"Crossref","is-referenced-by-count":14,"title":["Actions of Parathyroid Hormone Ligand Analogues in Humanized PTH1R Knockin Mice"],"prefix":"10.1210","volume":"163","author":[{"given":"Eileen J","family":"Daley","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Hee","family":"Yoon","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , 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General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T","family":"Potts","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry M","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc N","family":"Wein","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Lanske","sequence":"additional","affiliation":[{"name":"Radius Health Inc , Boston, Massachusetts 02210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2163-5772","authenticated-orcid":false,"given":"Thomas J","family":"Gardella","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Endocrine Unit, Massachusetts General Hospital , Boston, Massachusetts 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,4,23]]},"reference":[{"issue":"12","key":"2022060418140871200_CIT0001","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nrd.2017.178","article-title":"Trends in GPCR drug discovery: new agents, targets and indications","volume":"16","author":"Hauser","year":"2017","journal-title":"Nat Rev Drug Discov."},{"issue":"4","key":"2022060418140871200_CIT0002","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1124\/mol.117.111062","article-title":"G protein-coupled receptors as targets for approved drugs: how many targets and how many drugs?","volume":"93","author":"Sriram","year":"2018","journal-title":"Mol Pharmacol."},{"issue":"4","key":"2022060418140871200_CIT0003","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1210\/endrev\/bnab005","article-title":"Physiological and pharmacological roles of PTH and PTHrP in bone using their shared receptor, 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